Aspiration catheter systems and methods of use

ABSTRACT

Methods, systems, and devices for facilitation of intraluminal medical procedures within the neurovasculature including a catheter advancement element an inner diameter that is at least about 0.014″ up to about 0.024″ and an outer diameter having at least one snug point. A difference between the inner diameter of the distal, catheter portion and the outer diameter of the tubular portion at the snug point is no more than about 0.010″. A tip portion located distal to the at least one snug point of the tubular portion has a length and tapers along at least a portion of the length of the tip portion, wherein the tip portion has a distal point located a distance of at least 5 mm proximal from the distal-most end of the catheter advancement element, the distal point having a bending force that is no greater than about 0.05 Newtons.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of co-pending U.S. patentapplication Ser. No. 16/414,532, filed May 16, 2019, which claims thebenefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional PatentApplication Ser. No. 62/673,009, filed May 17, 2018. The disclosures arehereby incorporated by reference in their entireties.

FIELD

The present technology relates generally to medical devices and methods,and more particularly, to aspiration catheter systems and their methodsof use.

BACKGROUND

Acute ischemic stroke (AIS) usually occurs when an artery to the brainis occluded, preventing delivery of fresh oxygenated blood from theheart and lungs to the brain. These occlusions are typically caused by athrombus or an embolus lodging in the artery and blocking the arterythat feeds a territory of brain tissue. If an artery is blocked,ischemia injury follows, and brain cells may stop working. Furthermore,if the artery remains blocked for more than a few minutes, the braincells may die, leading to permanent neurological deficit or death.Therefore, immediate treatment is critical.

Two principal therapies are employed for treating ischemic stroke:thrombolytic therapy and endovascular treatment. The most commontreatment used to reestablish flow or re-perfuse the stroke territory isthe use of intravenous (IV) thrombolytic therapy. The timeframe to enactthrombolytic therapy is within 3 hours of symptom onset for IV infusion(4.5 hours in selected patients) or within 6 hours for site-directedintra-arterial infusion. Instituting therapy at later times has noproven benefit and may expose the patient to greater risk of bleedingdue to the thrombolytic effect. Endovascular treatment most commonlyuses a set of tools to mechanically remove the embolus, with our withoutthe use of thrombolytic therapy.

The gamut of endovascular treatments include mechanical embolectomy,which utilizes a retrievable structure, e.g., a coil-tipped retrievablestent (also known as a stent retriever or a STENTRIEVER), a woven wirestent, or a laser cut stent with struts that can be opened within a clotin the cerebral anatomy to engage the clot with the stent struts, createa channel in the emboli to restore a certain amount of blood flow, andto subsequently retrieve the retrievable structure by pulling it out ofthe anatomy, along with aspiration techniques. Other endovasculartechniques to mechanically remove AIS-associated embolus include ManualAspiration Thrombectomy (MAT) (also known as the “ADAPT” technique).ADAPT/MAT is an endovascular procedure where large bore catheters areinserted through the transfemoral artery and maneuvered through complexanatomy to the level of the embolus, which may be in the extracranialcarotids, vertebral arteries, or intracranial arteries. Aspirationtechniques may be used to remove the embolus through the large borecatheters. Another endovascular procedure is STENTRIEVER-Mediated ManualAspiration Thrombectomy (SMAT) (similar to the STENTRIEVER-assisted“Solumbra” technique). SMAT, like MAT, involves accessing the embolusthrough the transfemoral artery. After access is achieved, however, aretrievable structure is utilized to pull the embolus back into a largebore catheter.

To access the cerebral anatomy, guide catheters or guide sheaths areused to guide interventional devices to the target anatomy from anarterial access site, typically the femoral artery. The length of theguide is determined by the distance between the access site and thedesired location of the guide distal tip. Interventional devices such asguidewires, microcatheters, and intermediate catheters used forsub-selective guides and aspiration, are inserted through the guide andadvanced to the target site. Often, devices are used in a co-axialfashion, namely, a guidewire inside a microcatheter inside anintermediate catheter is advanced as an assembly to the target site in astepwise fashion with the inner, most atraumatic elements, advancingdistally first and providing support for advancement of the outerelements. The length of each element of the coaxial assemblage takesinto account the length of the guide, the length of proximal connectorson the catheters, and the length needed to extend from the distal end.

Typical tri-axial systems such as for aspiration or delivery of stentretrievers and other interventional devices require overlapped series ofcatheters, each with their own rotating hemostatic valves (RHV) on theproximal end. For example, a guidewire can be inserted through aPenumbra Velocity microcatheter having a first proximal RHV, which canbe inserted through a Penumbra ACE68 having a second proximal RHV, whichcan be inserted through a Penumbra NeuronMAX 088 access catheter havinga third proximal RHV positioned in the high carotid via a femoralintroducer. Maintaining the coaxial relationships between thesecatheters can be technically challenging. The three RHVs must beconstantly adjusted with two hands or, more commonly, four hands (i.e.two operators). Further, the working area of typical tri-axial systemsfor aspiration and/or intracranial device delivery can require workingarea of 3-5 feet at the base of the operating table.

The time required to access the site of the occlusion and restore, evenpartially, flow to the vessel is crucial in determining a successfuloutcome of such procedures. Similarly, the occurrence of distal emboliduring the procedure and the potentially negative neurologic effect andprocedural complications such as perforation and intracerebralhemorrhage are limits to success of the procedure. There is a need for asystem of devices and methods that allow for rapid access, optimizedcatheter aspiration and treatment to fully restore flow to the blockedcerebral vessel.

SUMMARY

In an aspect described is a coaxial catheter system including a catheterand a catheter advancement element. The catheter includes a distal,catheter portion having a lumen and a distal end having an opening fromthe lumen, the lumen having an inner diameter at the distal end of atleast about 0.052″; and a proximal extension coupled to and extendingproximally from the distal, catheter portion, the proximal extensionbeing less flexible than the distal, catheter portion. The catheteradvancement element includes a tubular portion having an inner diameterthat is at least about 0.014″ up to about 0.024″ and an outer diameterhaving at least one snug point. A difference between the inner diameterof the distal, catheter portion and the outer diameter of the tubularportion at such snug point is no more than about 0.010″. The catheteradvancement element includes a proximal extension coupled to andextending proximally from the tubular portion, the proximal extensionbeing less flexible than the tubular portion; and a tip portion locateddistal to the at least one snug point of the tubular portion. The tipportion has a length and tapers along at least a portion of the lengthof the tip portion. The coaxial catheter system has an advancementconfiguration characterized by the catheter advancement elementpositioned coaxially within the lumen of the distal catheter portion,the at least one snug point of the tubular portion is substantiallyaligned with the distal end of the distal catheter portion. Theadvancement configuration is also characterized by the tip portion inthe advancement configuration has at least three points spaced along thelength of the tip portion. The at least three points include a distalpoint of the at least three points located a distance proximal from thedistal-most end of the catheter advancement element, the distal pointhaving a first bending force that is no greater than about 0.05 Newtons;an intermediate point of the at least three points located a distanceproximal from the distal point, the intermediate point having a secondbending force; and a proximal point of the at least three points locateda distance proximal from the intermediate point, the proximal pointhaving a third bending force. The advancement configuration is alsocharacterized by the coaxial system having at least two system pointsalong a length of the coaxial system. The at least two system pointsinclude a first system point of the at least two system points locatedproximal to the distal end of the catheter portion, the first systempoint having a first system bending force; and a second system point ofthe at least two system points located distal to the first system pointby a distance that is at least about 1 mm distal to the distal end ofthe catheter portion, wherein the second system point can be the same ordifferent from the proximal point, the second system point having asecond system bending force.

A difference between the second bending force and the first bendingforce divided by the distance between the distal point and theintermediate point can equal a first flexibility slope. A differencebetween the third bending force and the second bending force divided bya distance between the intermediate point and the proximal point canequal a second flexibility slope. An average of the first flexibilityslope and the second flexibility slope can define an average tip portionflexibility slope. A difference between the first system bending forceand the second system bending force divided by the distance between thefirst system point and the second system point can equal a thirdflexibility slope. A ratio of the third flexibility slope to the averagetip portion flexibility slope can be less than about 25.

The proximal extension of the catheter advancement element can have atleast one stiffness point located within about 125 cm from thedistal-most end of the catheter advancement element, the at least onestiffness point has a bending force. A ratio of the bending force of theat least one stiffness point to the first bending force of the distalpoint can be at least about 100. The proximal extension of the catheteradvancement element can have at least one stiffness point located withinabout 125 cm from the distal-most end of the catheter advancementelement, the at least one stiffness point has a bending force, wherein aratio of the bending force of the at least one stiffness point to thefirst bending force of the distal point is at least about 200. Theproximal extension of the catheter advancement element can have at leastone stiffness point located within about 125 cm from the distal-most endof the catheter advancement element, the at least one stiffness pointhas a bending force. A ratio of the bending force of the at least onestiffness point to the first bending force of the distal point can begreater than at least about 300. The length of the tip portion can be atleast about 1 cm up to about 4 cm. A ratio of the third bending force ofthe proximal point to the first bending force of the distal point can beat least 2. A ratio of the first system bending force to the firstbending force of the distal point can be at least 2. The distal,catheter portion can have a catheter point located a distance of atleast 5 mm proximal from the distal end, the catheter point having acatheter bending force. The first bending force of the distal point canbe about 5%-15% the catheter bending force. The third bending force ofthe proximal point can be about 50%-90% the catheter bending force. Adifference between the first bending force at the distal point to thethird bending force at the proximal point can be a function of wallthickness. The inner diameter at the distal end of the distal, catheterportion can be about 0.054″ and the difference at the snug point can beabout 0.006″ to about 0.008″. The inner diameter at the distal end ofthe distal, catheter portion can be about 0.070″ up to about 0.088″ andthe difference at the snug point can be no more than about 0.006″ toabout 0.008″.

The tubular portion of the catheter advancement element can have aradiopaque marker band embedded within or positioned over a wall of thetubular portion, the radiopaque marker band positioned at the snugpoint. The radiopaque marker band can have a proximal edge, a distaledge, and a width between the proximal edge and the distal edge. When inthe advancement configuration, the proximal edge of the radiopaquemarker band can align substantially with the distal end of the distal,catheter portion such that the radiopaque marker band remains externalto the lumen of the distal, catheter portion. The outer diameter of thetubular portion can have a length that is at least about 5 cm up toabout 10 cm. The snug point can be located along at least a portion ofthe length. The outer diameter can be substantially uniform along thelength. The outer diameter can be substantially non-uniform along thelength. The distal point can be located a distance of at least 5 mmproximal from the distal-most end of the catheter advancement element.The first system point can be located at least about 5 mm proximal tothe distal end of the catheter portion.

In an interrelated aspect, described is a coaxial catheter systemincluding a catheter and a catheter advancement element. The catheterincludes a distal, catheter portion having a lumen and a distal endhaving an opening from the lumen, the lumen having an inner diameter atthe distal end of at least about 0.052″. The catheter includes aproximal extension coupled to and extending proximally from the distal,catheter portion, the proximal extension being less flexible than thedistal, catheter portion. The catheter advancement element includes atubular portion having an inner diameter that is at least about 0.014″up to about 0.024″, an outer diameter. The outer diameter has at leastone snug point. A difference between the inner diameter of the distal,catheter portion and the outer diameter of the tubular portion at thesnug point is no more than about 0.010″. The catheter advancementelement includes a tip portion located distal to the at least one snugpoint of the tubular portion. The tip portion has a length and tapersalong at least a portion of the length of the tip portion. The tipportion has a distal point located a distance of at least 5 mm proximalfrom the distal-most end of the catheter advancement element, the distalpoint having a bending force that is no greater than about 0.05 Newtons.

In an interrelated aspect, described is a method of performing a medicalprocedure in a cerebral vessel of a patient. The method includesadvancing a first assembled coaxial system of devices toward anocclusion within a cerebral blood vessel. The first assembled coaxialsystem of device includes a first catheter having a first catheterportion having a lumen, a proximal opening into the lumen, a distalopening from the lumen, and a distal end. A first proximal extension iscoupled to and extending proximally from the first catheter portion, thefirst proximal extension being less flexible than the first catheterportion. The first assembled coaxial system of device includes a firstdelivery element having a flexible, elongate body and a soft, tapereddistal tip portion. At least a portion of the elongate body positionedwithin the lumen of the first catheter portion and the tapered distaltip portion extending distal to the distal end of the first catheterportion. The method includes withdrawing the first delivery elementproximally from the lumen of the first catheter portion and advancing asecond assembled coaxial system of devices through the lumen of thefirst catheter portion, out the distal opening from the lumen, and to alocation near a proximal face of the occlusion within the cerebral bloodvessel. The second assembled coaxial system of devices includes a secondcatheter and a second delivery element. The second catheter includes asecond catheter portion having a lumen, a proximal opening into thelumen, a distal opening from the lumen, and a distal end; and a secondproximal extension coupled to and extending proximally from the secondcatheter portion, the second proximal extension being less flexible thanthe second catheter portion. The second delivery element includes aflexible, elongate body and a soft, tapered distal tip portion, at leasta portion of the elongate body positioned within the lumen of the secondcatheter portion and the tapered distal tip portion extending distal tothe distal end of the second catheter portion. The second assembledcoaxial system of devices is advanced together after the distal end ofthe second catheter portion is distal to the petrous portion of theinternal carotid artery. The method includes withdrawing the seconddelivery element proximally from the lumen of the second catheterportion; applying aspiration pressure through the lumen of the secondcatheter portion; anchoring the distal end of the second catheterportion onto the occlusion via the aspiration pressure; and applying aproximally-directed force on the second catheter to reduce slack in thesecond catheter relative to surrounding anatomy while the distal end ofthe second catheter portion remains anchored onto the occlusion.

The method can further include withdrawing the second catheter from thecerebral blood vessel, the distal end of the second catheter portion hasattached occlusive material. The method can further include advancingthe first catheter over the second catheter while anchoring the distalend of the second catheter portion onto the occlusion via the aspirationpressure. The method can further include positioning the distal end ofthe first catheter portion near the proximal face of the occlusion. Themethod can further include withdrawing the second catheter into thelumen of the first catheter; and automatically applying aspirationpressure through the lumen of the first catheter portion upon withdrawalof the second catheter into the lumen. The aspiration pressure appliedthrough the lumen of the first catheter portion and the lumen of thesecond catheter portion can be applied from a single source ofaspiration. The distal end of the second catheter portion can beattached occlusive material.

The method can further include withdrawing the second catheter from thelumen of the first catheter while the first catheter maintains theaspiration pressure through the lumen of the first catheter portion. Themethod can further include advancing a guide sheath from an accesslocation, wherein the guide sheath comprises a tubular sheath bodyhaving a central lumen, a proximal end, a distal opening, and aconnector operably connected with the proximal end of the sheath body.Advancing the first assembled coaxial catheter system can includeadvancing the first assembled coaxial catheter system through the guidesheath. The first catheter portion can have an outer diameter configuredto seal with the central lumen of the guide sheath upon application ofthe aspiration pressure. The second catheter portion can have an outerdiameter configured to seal with the lumen of the first catheter uponapplication of the aspiration pressure. An outer surface of the secondcatheter portion can seal with an inner surface of the first catheterportion forming a contiguous lumen between the distal opening of thesecond catheter portion to the proximal end of the guide sheath. Theconnector can include a single or two-headed rotating hemostatic valve.Both the first and second assembled coaxial catheter systems can beadvanced through the connector. The method can further include advancingthe guide sheath comprises advancing the distal opening of the guidesheath to a location in a distal internal carotid artery (ICA). Thesecond catheter can have an inner diameter that is between 0.054″ and0.070″, the first catheter has an inner diameter between 0.072″ and0.088″, and the guide sheath is between 6 Fr to 8 Fr. The method canfurther include advancing a guidewire across the occlusion. Theocclusion need not be penetrated during the method. The first assembledcoaxial catheter system can further include a guidewire. When assembled,the guidewire can be positioned within a lumen of the flexible, elongatebody of the first delivery element and the first delivery element can bepositioned within the lumen of the first catheter portion such that thetapered distal tip portion extends distal to the distal end of the firstcatheter portion and the guidewire extends distal to the tapered distaltip portion. An outer surface of the second catheter portion can sealwith an inner surface of the first catheter portion forming a contiguouslumen between the distal opening of the second catheter portion and theproximal opening of the first catheter portion.

In an interrelated aspect, described is a method of performing a medicalprocedure in a cerebral vessel of a patient. The method includesadvancing a first assembled coaxial catheter system to a location near aproximal face of an occlusion within a cerebral blood vessel. The firstassembled coaxial catheter system includes a first catheter and a firstdelivery element. The first catheter includes a first catheter portionhaving a lumen, a proximal opening into the lumen, a distal opening fromthe lumen, and a distal end; and a first proximal extension coupled toand extending proximally from the first catheter portion, the firstproximal extension being less flexible than the first catheter portion.The first delivery element includes a flexible, elongate body and asoft, tapered distal tip portion, at least a portion of the elongatebody positioned within the lumen of the first catheter portion and thetapered distal tip portion extending distal to the distal end of thefirst catheter portion. The first assembled coaxial system of devices isadvanced together after the distal end of the first catheter portion isdistal to the petrous portion of the internal carotid artery. The methodincludes withdrawing the first delivery element proximally from thelumen of the first catheter portion; applying aspiration pressurethrough the lumen of the first catheter portion; anchoring the distalend of the first catheter portion onto the occlusion via the aspirationpressure; applying a proximally-directed force on the first catheter toreduce slack in the first catheter relative to surrounding anatomy whilethe distal end of the first catheter remains anchored onto theocclusion; and advancing a second catheter over the first catheter whileanchoring the distal end of the first catheter portion onto theocclusion via the aspiration pressure. The second catheter includes asecond catheter portion having a lumen, a proximal opening into thelumen, a distal opening from the lumen, and a distal end; and a secondproximal extension coupled to and extending proximally from the secondcatheter portion. The second proximal extension is less flexible thanthe second catheter portion.

The method can further include withdrawing the first catheter from thecerebral blood vessel. The distal end of the first catheter portion mayhave attached occlusive material. The method can further includepositioning the distal end of the second catheter portion near theproximal face of the occlusion. The method can further includewithdrawing the first catheter into the lumen of the second catheter;and automatically applying aspiration pressure through the lumen of thesecond catheter portion upon withdrawal of the first catheter into thelumen. The aspiration pressure can be applied through the lumen of thefirst catheter portion and the lumen of the second catheter portion isapplied from a single source of aspiration. The distal end of the firstcatheter can have attached occlusive material. The method can furtherinclude withdrawing the first catheter from the lumen of the secondcatheter while the second catheter maintains the aspiration pressurethrough the lumen of the second catheter portion. The method can furtherinclude advancing a guide sheath from an access location. The guidesheath can include a tubular sheath body having a central lumen, aproximal end, a distal opening, and a connector operably connected withthe proximal end of the sheath body. The second catheter portion caninclude an outer diameter configured to seal with the central lumen ofthe guide sheath upon application of the aspiration pressure. The firstcatheter portion can have an outer diameter configured to seal with thelumen of the second catheter upon application of the aspirationpressure. An outer surface of the first catheter portion can seal withan inner surface of the second catheter portion forming a contiguouslumen between the distal opening of the first catheter portion to theproximal end of the guide sheath. The connector can include a single ortwo-headed rotating hemostatic valve. Both the first assembled coaxialcatheter system and the second catheter can be advanced through theconnector.

The method can include advancing the guide sheath comprises advancingthe distal opening of the guide sheath to a location in a distalinternal carotid artery (ICA). The first catheter can have an innerdiameter between 0.054″ and 0.070″. The second catheter can have aninner diameter between 0.072″ and 0.088″. The guide sheath can bebetween 6 Fr to 8 Fr. The method can further include advancing aguidewire across the occlusion. The occlusion need not be penetratedduring the method. An inner surface of the second catheter portion canseal with an outer surface of the first catheter portion forming acontiguous aspiration lumen between the distal opening of the firstcatheter portion and the proximal opening of the second catheterportion.

In an interrelated aspect, disclosed is a system of devices forperforming a medical procedure in a cerebral vessel of a patientincluding a first catheter and a second catheter. The first catheterincludes a first catheter portion having a lumen, a proximal openinginto the lumen, a distal opening from the lumen, and a distal end; and afirst proximal extension coupled to and extending proximally from thefirst catheter portion, the first proximal extension being less flexiblethan the first catheter portion. The second catheter is configured to becoaxially disposed within the lumen of the first catheter portion. Thesecond catheter includes a second catheter portion having a lumen, aproximal opening into the lumen, a distal opening from the lumen, and adistal end; and a second proximal extension coupled to and extendingproximally from the second catheter portion, the second proximalextension being less flexible than the second catheter portion. Thesystem includes a guide sheath having a tubular sheath body with acentral lumen, a proximal end, a distal opening, and a connectoroperably connected with the proximal end of the sheath body. A single,shared vacuum source is coupled to the connector of the guide sheath andconfigured to apply aspiration pressure through the central lumen of theguide sheath, the lumen of the first catheter portion, and the lumen ofthe second catheter portion. An outer surface of the second catheterportion can seal with an inner surface of the first catheter portionforming a contiguous lumen between the distal opening of the firstcatheter portion and the proximal opening of the second catheterportion.

In an interrelated aspect, disclosed is a method of performing a medicalprocedure in a cerebral vessel of a patient. The method includesadvancing a first catheter towards an occlusion within a cerebral bloodvessel. The first catheter includes a first catheter portion having alumen, a proximal opening into the lumen, a distal opening from thelumen, and a distal end; and a first proximal extension coupled to thefirst catheter portion near the proximal opening, the first proximalextension being less flexible than the first catheter portion. Themethod includes advancing a second catheter through the lumen of thefirst catheter portion, out the distal opening from the lumen, and to alocation near a proximal face of the occlusion within the cerebral bloodvessel. The second catheter includes a second catheter portion having alumen, a proximal opening into the lumen, a distal opening from thelumen, and a distal end; and a second proximal extension coupled to thesecond catheter portion near the proximal opening, the second proximalextension being less flexible than the second catheter portion. Themethod includes forming a seal between an outer diameter of the secondcatheter portion and an inner diameter of the first catheter portion;and applying aspiration pressure through at least one of the lumen ofthe second catheter portion, the lumen of the first catheter portion, ora contiguous aspiration lumen formed by the lumens of the first andsecond catheter portions. The contiguous aspiration lumen extends fromthe distal end of the second catheter portion towards the proximalopening of the first catheter portion. The method can further includeanchoring the distal end of the second catheter portion onto theocclusion via the aspiration pressure. The method can further includeapplying a proximally-directed force on the second catheter to reduceslack in the second catheter relative to surrounding anatomy while thedistal end of the second catheter portion remains anchored onto theocclusion.

In some variations, one or more of the following can optionally beincluded in any feasible combination in the above methods, apparatus,devices, and system. More details of the methods, apparatus, devices,and systems are set forth in the accompanying drawings and thedescription below. Other features and advantages will be apparent fromthe description and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects will now be described in detail with referenceto the following drawings. Generally speaking the figures are not toscale in absolute terms or comparatively, but are intended to beillustrative. Also, relative placement of features and elements may bemodified for the purpose of illustrative clarity.

FIGS. 1A-1B illustrate the course of the terminal internal carotidartery through to the cerebral vasculature;

FIG. 1C illustrates the aortic arch including the take-offs of thebrachiocephalic BT, left common carotid LCC, and left subclavianarteries LSA from the aortic arch AA;

FIG. 2A is an exploded view of an implementation of an aspirationcatheter system;

FIG. 2B is an assembled view of the aspiration catheter system of FIG.2A;

FIG. 2C is a detail view of FIG. 2A taken at circle C-C;

FIG. 2D illustrates an implementation of an arterial access devicehaving a distal occlusion balloon;

FIG. 3 is a side view of an implementation of a spined distal accesscatheter;

FIG. 4A is a cross-sectional view of first implementation of a proximalcontrol element of a spined distal access catheter;

FIG. 4B is a cross-sectional view of another implementation of aproximal control element of a spined distal access catheter;

FIG. 4C is a cross-sectional view of the proximal control element ofFIG. 4A within a working lumen of an access sheath;

FIG. 4D is a cross-sectional view of the proximal control element ofFIG. 4B within a working lumen of an access sheath having a catheteradvancement element extending therethrough;

FIG. 4E is a cross-sectional, schematic view comparing the surface areaof the proximal control element of FIG. 4A and the proximal controlelement of FIG. 4B within the working lumen of an access sheath of FIG.4D;

FIGS. 4F-4G are cross-sectional, schematic views comparing trapezoid-and D-shaped proximal extensions, respectively, relative to a workinglumen of an access sheath;

FIG. 5A is a side elevational view of an implementation of a spineddistal access catheter;

FIG. 5B is a top plan view of the spined distal access catheter of FIG.5A;

FIG. 5C is a cross-sectional view of the spined distal access cathetertaken along line C-C of FIG. 5B;

FIG. 5D is a cross-sectional view of the spined distal access cathetertaken along line D-D of FIG. 5B;

FIGS. 5E-5F are partial perspective views of the spined distal accesscatheter of FIG. 5A;

FIG. 6A is a side elevational view of an implementation of a spineddistal access catheter;

FIG. 6B is a top plan view of the spined distal access catheter of FIG.6A;

FIG. 6C is a cross-sectional view of the spined distal access cathetertaken along line C-C of FIG. 6B;

FIG. 6D is a cross-sectional view of the spined distal access cathetertaken along line D-D of FIG. 6B;

FIGS. 6E-6F are partial perspective views of the spined distal accesscatheter of FIG. 6A;

FIG. 7A is a side view of an implementation of a catheter advancementelement;

FIG. 7B is a cross-sectional view of the catheter advancement element ofFIG. 7A;

FIG. 7C is a detail view of FIG. 7B taken along circle C-C;

FIG. 7D is a side view of another implementation of a catheteradvancement element;

FIG. 7E is cross-sectional view of an implementation of a proximalportion the catheter advancement element of FIG. 7D;

FIGS. 7F-7J are various views of an implementation of a proximal hub forcoupling to the proximal portion shown in FIG. 7E;

FIG. 8A is a side view of an implementation of a catheter;

FIG. 8B is a schematic cut-away view of the distal end region of thecatheter of FIG. 8A;

FIG. 8C is a schematic cross-sectional view of the distal end region ofthe catheter of FIG. 8A;

FIGS. 9A-9C are various views of a proximal extension connector;

FIG. 10A is a schematic cross-sectional view of an implementation of acatheter advancement element;

FIG. 10B is a schematic cross-sectional view of a distal end region ofthe catheter advancement element of FIG. 10A;

FIG. 10C is a schematic cross-sectional view of a middle region of thecatheter advancement element of FIG. 10A;

FIG. 11 is a schematic of an implementation of a catheter aligned withan implementation of a catheter advancement element illustratingstaggered material transitions;

FIG. 12 is a schematic of an implementation of a bending force testingsystem;

FIG. 13A is a schematic of a distal end region of a catheter advancementelement extending through a catheter and points tested for bendingforce;

FIG. 13B illustrates bending force in Newtons (N) along a length of acatheter system including a catheter and a catheter advancement elementin the advancement configuration (hashed line), the catheter advancementelement alone (hash-dot-hash line), and the catheter alone (solid line);

FIG. 14A is a graph of the bending forces along a length of a cathetersystem formed of a catheter advancement element configured to extendthrough a catheter having an inner diameter of 0.054″;

FIG. 14B is a graph of the bending forces along a length of a cathetersystem formed of a catheter advancement element configured to extendthrough a catheter having an inner diameter of 0.070″;

FIG. 14C is a graph of the bending forces along a length of a cathetersystem formed of a catheter advancement element configured to extendthrough a catheter having an inner diameter of 0.070″;

FIG. 14D is a graph of the bending forces along a length of a cathetersystem formed of a catheter advancement element configured to extendthrough a catheter having an inner diameter of 0.088″;

FIG. 14E is a graph of the bending forces along a length of anothercatheter system;

FIG. 15 illustrates an implementation of a nested catheter system.

It should be appreciated that the drawings are for example only and arenot meant to be to scale. It is to be understood that devices describedherein may include features not necessarily depicted in each figure.

DETAILED DESCRIPTION

Navigating the carotid anatomy in order to treat various neurovascularpathologies at the level of the cerebral arteries, such as acuteischemic stroke (AIS), requires catheter systems having superiorflexibility and deliverability. The internal carotid artery (ICA) arisesfrom the bifurcation of the common carotid artery (CCA) at the level ofthe intervertebral disc between C3 and C4 vertebrae. As shown in FIG.1A, the course of the ICA is divided into four parts—cervical Cr,petrous Pt, cavernous Cv and cerebral Cb parts. In the anteriorcirculation, the consistent tortuous terminal carotid is locked into itsposition by bony elements. The cervical carotid Cr enters the petrousbone and is locked into a set of turns as it is encased in bone. Thecavernous carotid is an artery that passes through a venous bed, thecavernous sinus, and while flexible, is locked as it exits the cavernoussinus by another bony element, which surrounds and fixes the entry intothe cranial cavity. Because of these bony points of fixation, thepetrous and cavernous carotid (Pt and Cv) and above are relativelyconsistent in their tortuosity. The carotid siphon CS is an S-shapedpart of the terminal ICA. The carotid siphon CS begins at the posteriorbend of the cavernous ICA and ends at the ICA bifurcation into theanterior cerebral artery ACA and middle cerebral artery MCA. Theophthalmic artery arises from the cerebral ICA, which represents acommon point of catheter hang-up in accessing the anterior circulation.The MCA is initially defined by a single M1 segment and then furtherbifurcates in two or three M2 segments and then further arborizes tocreate M3 segments. These points of catheter hang-up can significantlyincrease the amount of time needed to restore blood perfusion to thebrain, which in the treatment of AIS is a disadvantage with severeconsequences.

With advancing age, the large vessels often enlarge and lengthen. Fixedproximally and distally, the cervical internal carotid artery oftenbecomes tortuous with age. The common carotid artery CCA is relativelyfixed in the thoracic cavity as it exits into the cervical area by theclavicle. The external and internal carotid arteries ECA, ICA are notfixed relative to the common carotid artery CCA, and thus they developtortuosity with advancing age with lengthening of the entire carotidsystem. This can cause them to elongate and develop kinks and tortuosityor, in worst case, a complete loop or so-called “cervical loop”. Ifcatheters used to cross these kinked or curved areas are too stiff orinflexible, these areas can undergo a straightening that can cause thevessel to wrap around or “barbershop pole” causing focused kinking andfolding of the vessel. These sorts of extreme tortuosity also cansignificantly increase the amount of time needed to restore bloodperfusion to the brain, particularly in the aging population. In certaincircumstances, the twisting of vessels upon themselves or if theuntwisted artery is kinked, normal antegrade flow may be reduced to astandstill creating ischemia. Managing the unkinking or unlooping thevessels such as the cervical ICA can also increase the time it takes toperform a procedure.

A major drawback of current catheter systems for stroke interventionprocedures is the amount of time required to restore blood perfusion tothe brain, including the time it takes to access the occlusive site orsites in the cerebral artery and the time it takes to completely removethe occlusion in the artery. Because it is often the case that more thanone attempt must be made to completely remove the occlusion, reducingthe number of attempts as well as reducing the time required to exchangedevices for additional attempts is an important factor in minimizing theoverall time. Additionally, each attempt is associated with potentialprocedural risk due to device advancement in the delicate cerebralvasculature. Another limitation is the need for multiple operators todeliver and effectively manipulate long tri-axial systems with multipleRHVs typically used with conventional guide and distal access catheters.

Described herein are catheter systems and methods for treating variousneurovascular pathologies, such as acute ischemic stroke (AIS). Thesystems described herein provide quick and simple single-operator accessto distal target anatomy, in particular tortuous anatomy of the cerebralvasculature at a single point of manipulation. The medical methods,devices and systems described herein allow for navigating complex,tortuous anatomy to perform rapid and safe aspiration and removal ofcerebral occlusions for the treatment of acute ischemic stroke. Themedical methods, devices and systems described herein can also be usedto deliver intracranial medical devices, with or without aspiration forthe removal of cerebral occlusions in the treatment of acute ischemicstroke. The systems described herein can be particularly useful for thetreatment of AIS whether a user intends to perform aspiration alone as afrontline treatment for AIS. Further, the extreme flexibility anddeliverability of the distal access catheter systems described hereinallow the catheters to take the shape of the tortuous anatomy ratherthan exert straightening forces creating new anatomy. The distal accesscatheter systems described herein can pass through tortuous loops whilemaintaining the natural curves of the anatomy therein decreasing therisk of vessel straightening. The distal access catheter systemsdescribed herein can thereby create a safe conduit through theneurovasculature maintaining the natural tortuosity of the anatomy forother catheters to traverse (e.g. larger bore aspiration catheters).

The devices, systems, and methods of use described herein are related toand can be used in combination and in the alternative with the devices,systems, and methods of use described in U.S. Publication No.2013/0035628, filed Aug. 3, 2012; U.S. Publication No. 2015/0173782,filed Dec. 19, 2014; and U.S. Publication No. 2016/0220741, filed Feb.4, 2016. The disclosures of each of these publications are incorporatedby reference herein in their entireties.

While some implementations are described herein with specific regard toaccessing a neurovascular anatomy for application of aspiration, thesystems and methods described herein should not be limited to this andmay also be applicable to other uses. For example, the catheter systemsdescribed herein may be used to deliver working devices to a targetvessel of a coronary anatomy or other vasculature anatomy. Where thephrase “distal access catheter” or “aspiration catheter” is used hereinthat the catheter can be used for aspiration, the delivery of fluids toa treatment site or as a support catheter, or distal access providing aconduit that facilitates and guides the delivery or exchange of otherdevices such as a guidewire or interventional devices such as stentretrievers. Alternatively, the access systems described herein may alsobe useful for access to other parts of the body outside the vasculature.Similarly, where the working device is described as being an expandablecerebral treatment device, stent retriever or self-expanding stent otherinterventional devices can be delivered using the delivery systemsdescribed herein.

Referring now to the drawings, FIGS. 2A-2B illustrate a system 100including devices for accessing and removing a cerebral occlusion totreat acute ischemic stroke. The system 100 can be a single operatorsystem such that each of the components and systems can be delivered andused together by one operator through a single point of manipulationrequiring minimal hand movements. As will be described in more detailbelow, all wire and catheter manipulations can occur at or in closeproximity to a single rotating hemostatic valve (RHV) 434 or more than asingle RHV co-located in the same device. The system 100 can include oneor more catheter delivery systems 150, each having a catheter 200 and acatheter advancement element 300. The catheter delivery system 150 isconfigured to be advanced through an access guide sheath 400. Thecatheter 200 is configured to be received through the guide sheath 400and is designed to have exceptional deliverability. The catheter 200 canbe a spined, distal access catheter co-axial with a lumen of the guidesheath 400 thereby providing a step-up in inner diameter within theconduit. The catheter 200 can be delivered using a catheter advancementelement 300 inserted through a lumen 223 of the catheter 200. The system100 can be a distal access system that can create a variable length frompoint of entry at the percutaneous arteriotomy (e.g. the femoral arteryor other point of entry) to the target control point of the distalcatheter. Conventional distal access systems for stroke interventiontypically include a long guide sheath or guide catheter placed through ashorter “introducer” sheath (e.g. 11-30 cm in length) at the groin. Thelong guide sheath is typically positioned in the ICA to supportneurovascular interventions including stroke embolectomy (sometimesreferred to as “thrombectomy”). For added support, these can be advancedup to the bony terminal petrous and rarely into the cavernous or clinoidor supraclinoid terminal ICA when possible. To reach targets in the M1or M2 distribution for ADAPT/MAT or Solumbra/SMAT approaches, anadditional catheter may be inserted through the long guide catheter.These catheters are typically large-bore aspiration catheters that canbe, for example 130 cm in length or longer. As will be described in moredetail below, the distal access systems 100 described herein can beshorter, for example, only 115 cm in length when taken as a system asmeasured from the access point, typically the common femoral artery.Additionally, the single operator can use the systems described hereinby inserting them through a single rotating hemostatic valve (RHV) 434on the guide sheath 400 or more than one RHV co-located in the samedevice such as a dual-headed RHV. Thus, what was once a two-personprocedure can be a one-person procedure.

Each of the various components of the various systems will now bedescribed in more detail.

Access Guide Sheath

Again with respect to FIGS. 2A-2D, the distal access system 100 caninclude an access guide sheath 400 having a body 402 through which aworking lumen extends from a proximal hemostasis valve 434 coupled to aproximal end region 403 of the body 402 to a distal opening 408 of adistal end region. The working lumen is configured to receive thecatheter 200 therethrough such that a distal end of the catheter 200 canextend beyond a distal end of the sheath 400 through the distal opening408. The guide sheath 400 can be used to deliver the catheters describedherein as well as any of a variety of working devices known in the art.For example, the working devices can be configured to provide thrombotictreatments and can include large-bore catheters, aspiration embolectomy(or thrombectomy), advanced catheters, wires, balloons, retrievablestructures such as coil-tipped retrievable stents “stent retriever”. Theguide sheath 400 in combination with the catheter 200 can be used toapply distal aspiration as will be described in more detail below.

The guide sheath 400 can be any of a variety of commercially availableguide sheaths. For example, the guide sheath 400 can have an ID between0.087″-0.089″ such as the Cook SHUTTLE 6F (Cook Medical, Inc.,Bloomington, Ind.), Terumo DESTINATION 6F (Terumo Europe NV), CordisVISTA BRITE TIP (Cordis Corp., Hialeah, Fla.), and Penumbra NEURON MAX088 (Penumbra, Inc., Alameda, Calif.), Stryker Infinity (StrykerNeurovascular, Fremont, Calif.) or comparable commercially availableguiding sheath. Generally, sheath sizes are described herein using theFrench (F) scale. For example, where a sheath is described as being 6French, the inner diameter of that sheath is able to receive a catheterhaving a 6F outer diameter, which is about 1.98 mm or 0.078″. A cathetermay be described herein as having a particular size in French to referto the compatibility of its inner diameter to receive an outer diameterof another catheter. A catheter may also be described herein as having aparticular size in French to refer to its outer diameter beingcompatible with another catheter having a particular inner diameter.

The guide sheath 400 can be a variety of sizes to accept various workingdevices, such as catheter 200, and can be accommodated to the operator'spreference. The working lumen of the guide sheath 400 can be sized toreceive its respective catheter 200 in a sliding fit. Generally, it isdesirable to minimize the overall size of the vessel insertion site bylimiting the outer diameter of the guide sheath 400 to under 0.122″. Itis also desirable to select corresponding outer and inner diameters toprovide a good sliding fit between the catheter 200 and the guide sheath400. The working lumen of the guide sheath may have an inner diameterthat is at least 0.001″ larger than a maximum outer diameter of anycatheter 200 it is intended to receive, particularly if the catheter 200is to be used for aspiration. The working lumen can have an innerdiameter sized to accommodate at least 6 French catheters (1.98 mm or0.078″), or at least 6.3 French catheters (2.079 mm or 0.082″ OD), or atleast 7 French (2.31 mm or 0.091″ OD) catheters or 8 French (2.64 mm or0.104″ OD) or larger catheters. The inner diameter of the guide sheath400, however, may be smaller or larger to be compatible with othercatheter sizes. Regardless of the length and inner diameter, the guidesheath 400 is resistant to kinking during distal advancement through thevessels.

The aspiration catheters described herein can have an ID of between0.054″ to 0.088″. If the catheter 200 has an 0.088″ inner diameter andhave a maximum outer diameter of between 0.105″ and 0.107″. The guidesheath 400 can, in turn, have a working lumen with an inner diameterthat is between 0.106″ and 0.108″. Generally, the difference orclearance between the maximum outer diameter of the catheter 200 and theinner diameter of the guide sheath 400 is less than about 0.002″, forexample between 0.001″ up to 0.002″. The region of low clearance betweenthe maximum outer diameter of the catheter 200 and the inner diameter ofthe guide sheath 400 can be limited to a localized region. Meaning, thelow clearance fit between the two can extend only a fraction of acylindrical length of the catheter 200 and the sheath 400. Thus, theOD-ID difference between the catheter 200 and the guide sheath 400 canbe greater than or equal to 0.002″ along a first cylindrical length ofwhere the two devices overlap during use and below 0.002″ along adifferent cylindrical length of the overlap, thereby providing alocalized region of low clearance within the overlap. This allows for aconvenient relative slidability and sufficient sealing when placed underaspiration pressure as will be described in more detail below. Forexample, a distal region of the guide sheath 400 can have a first innerdiameter at a distal end region and a second, different inner diameterat a proximal end region such that the low clearance of the sliding fitwith the catheter 200 varies along its length. In some implementations,the catheter 200 has a first outer diameter at a distal end region and asecond, larger outer diameter at a proximal end region. The second,larger outer diameter can be less than 0.002″ the inner diameter of thesheath 400 and the first outer diameter greater than 0.002″ the innerdiameter of the sheath 400. The provides a tighter overall fit betweenthe guide sheath 400 and the proximal end region of the catheter 200 atthe location of this second, larger outer diameter.

Again with respect to FIGS. 2A-2D, the sheath body 402 can extend from aproximal furcation or rotating hemostatic valve (RHV) 434 at a proximalend region 403 to a tip 406 at a distal end of the body 402. Theproximal RHV 434 may include one or more lumens molded into a connectorbody to connect to the working lumen of the body 402 of the guide sheath400. The working lumen can receive the catheter 200 and/or any of avariety of working devices for delivery to a target anatomy. The RHV 434can be constructed of thick-walled polymer tubing or reinforced polymertubing. The RHV 434 allows for the introduction of devices through theguide sheath 400 into the vasculature, while preventing or minimizingblood loss and preventing air introduction into the guide sheath 400.The RHV 434 can be integral to the guide sheath 400 or the guide sheath400 can terminate on a proximal end in a female Luer adaptor to which aseparate hemostasis valve component, such as a passive seal valve, aTuohy-Borst valve or rotating hemostasis valve may be attached. The RHV434 can have an adjustable opening that is open large enough to allowremoval of devices that have adherent clot on the tip without causingthe clot to dislodge at the RHV 434 during removal. Alternately, the RHV434 can be removable such as when a device is being removed from thesheath 400 to prevent clot dislodgement at the RHV 434. The RHV 434 canbe a dual RHV.

The RHV 434 can form a Y-connector on the proximal end 403 of the sheath400 such that the first port of the RHV 434 can be used for insertion ofa working catheter into the working lumen of the sheath 400 and a secondport into arm 412 can be used for another purpose. For example, asyringe or other device can be connected at arm 412 via a connector 432to deliver a forward drip, a flush line for contrast or salineinjections through the body 402 toward the tip 406 and into the targetanatomy. Arm 412 can also connect to an aspiration source 505 (see FIG.2B). The aspiration source 505 can be an active source of aspirationsuch as an aspiration pump, a regular or locking syringe, a hand-heldaspirator, hospital suction, or the like, configured to draw suctionthrough the working lumen. In an embodiment, the aspiration source 505is a locking syringe (for example a VacLok Syringe) attached to a flowcontroller. The plunger on the syringe can be pulled back into a lockedposition by the user while the connection to the flow line is closedprior to an embolectomy step of the procedure. During the procedure whenthe tip of the catheter is near or at the face of the occlusion, theuser may open the connection to the aspiration syringe. This allows fora maximum communication of aspiration force being applied through theworking lumen of the sheath 400 and any catheter extending through thesheath 400 that in turn is in communication with the vessel at itsdistal end. The aspiration can be applied in a rapid fashion by a singleuser at the single, shared source. In another implementations, the arm412 can be connected to an aspiration source 505 that is a pumpconfigured to apply an aspiration pressure through the working lumen ofthe guide sheath 400. The single, shared source of aspiration issufficient to draw aspiration through the entire system 100, even whenmultiple aspiration catheters 200 are nested within one another throughthe working lumen of the guide sheath 400. The arm 412 can also allowthe guide sheath 400 to be flushed with saline or radiopaque contrastduring a procedure. The working lumen can extend from a distal end to aworking proximal port of the proximal end region 403 of the sheath body402.

The length of the catheter body 402 is configured to allow the distaltip 406 of the body 402 to be positioned as far distal in the internalcarotid artery (ICA), for example, from a transfemoral approach, withadditional length providing for adjustments if needed. In someimplementations (e.g. femoral or radial percutaneous access), the lengthof the body 402 can be in the range of 80 to 90 cm or can be longer, forexample, up to about 100 cm or up to about 105 cm. In implementations,the body 402 length is suitable for a transcarotid approach to thebifurcation of the carotid artery, in the range of 20-25 cm. In furtherimplementations, the body 402 length is suitable for a percutaneoustranscarotid approach to the CCA or proximal ICA, and is in the range of10-15 cm. The body 402 is configured to assume and navigate the bends ofthe vasculature without kinking, collapsing, or causing vascular trauma,even, for example, when subjected to high aspiration forces.

In some implementations, the system 100 can further include a selecttool for advancing the guide sheath 400. The select tool can have anouter diameter configured to be received within the working lumen of theguide sheath 400 such that a distal end region of the select toolextends a distance distal to the distal end of the guide sheath 400. Theouter diameter of the select tool sufficiently fills the inner diameterof the working lumen of the guide sheath 400 to minimize the lip at thedistal opening 408 of the guide sheath 400. For example, if the workinglumen of the guide sheath 400 has an inner diameter that is betweenabout 0.087″ to about 0.113″, the outer diameter of the select tool canbe about 0.006″ less than this, or between about 0.081″ to about 0.107″.The brachiocephalic take-off (BT) is typically a very severe turn offthe aortic arch AA for a transfemorally-delivered catheter seeking theright-sided cerebral circulation (shown in FIG. 1C). A cathetertraverses from the femoral artery through the iliac circulation into thedescending aorta DA. The catheter turns as it approaches the aortic archAA and reaches across the take-off of other great vessels to reach thebrachiocephalic take-off (BT), which is the furthest “reach” of thegreat vessels of the aortic arch AA. FIG. 1C shows the substantial andobligatory S-turn created by that anatomy. A catheter must traverse thisS-turn along a path of insertion from a femoral artery insertionlocation in order to reach the internal carotid artery (ICA). The leftICA often takes off from the brachiocephalic and thus, has a similarchallenge and can create an even tighter S-turn. Should the left ICAhave a typical take-off between the brachiocephalic BT and the leftsubclavian artery LSA take-off, then the reach may be less severe, butan S-turn still develops of lesser severity. The distal end region ofthe select tool can be tapered and/or shaped to provide support andguidance to advance the sheath 400 around this turn into the ICA. Insome implementations, the select tool can have a Bernstein Select-styleor a Simmons-style reverse curve catheter tip as is known in the art.

The tip 406 of the guide sheath 400 can have a same or similar outerdiameter as a section of the body 402 leading up to the distal end.Accordingly, the tip 406 may have a distal face orthogonal to alongitudinal axis passing through the body 402 and the distal face mayhave an outer diameter substantially equal to a cross-sectional outerdimension of the body 402. In an implementation, the tip 406 includes achamfer, fillet, or taper, making the distal face diameter slightly lessthan the cross-sectional dimension of the body 402. In a furtherimplementation, the tip 406 may be an elongated tubular portionextending distal to a region of the body 402 having a uniform outerdiameter such that the elongated tubular portion has a reduced diametercompared to the uniform outer diameter of the body 402. Thus, the tip406 can be elongated or can be more bluntly shaped. Accordingly, the tip406 may be configured to smoothly track through a vasculature and/or todilate vascular restrictions as it tracks through the vasculature. Theworking lumen may have a distal end forming a distal opening 408.

The guide sheath 400 may include a tip 406 that tapers from a section ofthe body 402 leading up to the distal end. That is, an outer surface ofthe body 402 may have a diameter that reduces from a larger dimension toa smaller dimension at a distal end. For example, the tip 406 can taperfrom an outer diameter of approximately 0.114″ to about 0.035″ or fromabout 0.110″ to about 0.035″ or from about 0.106″ to about 0.035″. Theangle of the taper of the tip 406 can vary depending on the length ofthe tapered tip 406. For example, in some implementations, the tip 406tapers from 0.110″ to 0.035″ over a length of approximately 50 mm.

In an implementation, the guide sheath 400 includes one or moreradiopaque markers 411. The radiopaque markers 411 can be disposed nearthe distal tip 406. For example, a pair of radiopaque bands may beswaged, painted, embedded, or otherwise disposed in or on the body 402.In some implementations, the radiopaque markers 411 include a bariumpolymer, tungsten polymer blend, tungsten-filled or platinum-filledmarker that maintains flexibility of the distal end of the device andimproves transition along the length of the guide sheath 400 and itsresistance to kinking. In some implementations, the radiopaque marker411 is a tungsten-loaded PEBAX or polyurethane that is heat welded tothe body 402. The markers 411 are shown in the figures as rings around acircumference of one or more regions of the body 402. However, themarkers 411 can have other shapes or create a variety of patterns thatprovide orientation to an operator regarding the position of the distalopening 408 within the vessel. Accordingly, an operator may visualize alocation of the distal opening 408 under fluoroscopy to confirm that thedistal opening 408 is directed toward a target anatomy where a catheter200 is to be delivered. For example, radiopaque marker(s) 411 allow anoperator to rotate the body 402 of the guide sheath 400 at an anatomicalaccess point, e.g., a groin of a patient, such that the distal openingprovides access to an ICA by subsequent working device(s), e.g.,catheters and wires advanced to the ICA. In some implementations, theradiopaque marker(s) 411 include platinum, gold, tantalum, tungsten orany other substance visible under an x-ray fluoroscope. Any of thevarious components of the systems described herein can incorporateradiopaque markers.

In some implementations, the guide sheath 400 can have performancecharacteristics similar to other sheaths used in carotid access and AISprocedures in terms of kinkability, radiopacity, column strength, andflexibility. The inner liners can be constructed from a low frictionpolymer such as PTFE (polytetrafluoroethylene) or FEP (fluorinatedethylene propylene) to provide a smooth surface for the advancement ofdevices through the inner lumen. An outer jacket material can providemechanical integrity to the inner liners and can be constructed frommaterials such as PEBAX, thermoplastic polyurethane, polyethylene,nylon, or the like. The body 402 can include a hydrophilic coating. Athird layer can be incorporated that can provide reinforcement betweenthe inner liner and the outer jacket. The reinforcement layer canprevent flattening or kinking of the inner lumen of the body 402 toallow unimpeded device navigation through bends in the vasculature aswell as aspiration or reverse flow. The body 402 can becircumferentially reinforced. The reinforcement layer can be made frommetal such as stainless steel, Nitinol, Nitinol braid, helical ribbon,helical wire, cut stainless steel, or the like, or stiff polymer such asPEEK. The reinforcement layer can be a structure such as a coil orbraid, or tubing that has been laser-cut or machine-cut so as to beflexible. In another implementation, the reinforcement layer can be acut hypotube such as a Nitinol hypotube or cut rigid polymer, or thelike. The outer jacket of the body 402 can be formed of increasinglysofter materials towards the distal end. The flexibility of the body 402can vary over its length, with increasing flexibility towards the distalportion of the body 402. The variability in flexibility may be achievedin various ways. For example, the outer jacket may change in durometerand/or material at various sections. A lower durometer outer jacketmaterial can be used in a distal section of the guide sheath compared toother sections of the guide sheath. Alternately, the wall thickness ofthe jacket material may be reduced, and/or the density of thereinforcement layer may be varied to increase the flexibility. Forexample, the pitch of the coil or braid may be stretched out, or the cutpattern in the tubing may be varied to be more flexible. Alternately,the reinforcement structure or the materials may change over the lengthof the sheath body 402. In another implementation, there is a transitionsection between the distal-most flexible section and the proximalsection, with one or more sections of varying flexibilities between thedistal-most section and the remainder of the sheath body 402. In thisimplementation, the distal-most section is about 2 cm to about 5 cm, thetransition section is about 2 cm to about 10 cm and the proximal sectiontakes up the remainder of the sheath length. In some implementations,the proximal region of the body 402 can be formed of a material such asNylon, a region of the body 402 distal to the proximal region of thebody 402 can have a material hardness of 72D whereas areas more distalcan be increasingly more flexible and formed of materials having amaterial hardness of 55D, 45D, 35D extending towards the distal tip 406,which can be formed of a material having a material hardness of 35D, forexample.

The working lumen of the guide sheath 400 can have different innerdiameters configured to receive different outer diameter catheters 200.In some implementations, the working lumen of a first guide sheath 400can have an inner diameter sized to receive a 6F catheter and theworking lumen of a second guide sheath 400 can have an inner diametersized to receive a 8F catheter. The guide sheaths 400 can receivecatheters having an outer diameter along at least a length that is snugto the inner diameter dimension of the guide sheath 400. The guidesheath 400 (as well as any of the variety of components used incombination with the sheath 400) can be an over-the-wire (OTW) or rapidexchange type device, which will be described in more detail below.

The sheath 400 can include a body 402 formed of generally three layers,including a lubricious inner liner, a reinforcement layer, and an outerjacket layer. The reinforcement layer can include a braid to providegood torqueability optionally overlaid by a coil to provide good kinkresistance. In sheaths where the reinforcement layer is a braid alone,the polymers of the outer jacket layer can be generally higher durometerand thicker to avoid issues with kinking. The wall thickness of suchsheaths that are braid alone with thicker polymer can be about 0.011″.The wall thickness of the sheaths 400 described herein having a braidwith a coil overlay provide both torqueability and kink resistance andcan have a generally thinner wall, for example, a wall thickness ofabout 0.0085″. The proximal end outer diameter can thereby be reduced toless than 0.112″, for example, about 0.107″ outer diameter. It isgenerally beneficial to limit the overall OD of the guide sheath 400such that the entry wound into the patient (e.g. at the femoral artery)can be kept to a minimum size. Thus, the sheath 400 is a highperformance sheath 400 that has good torque and kink resistance with athinner wall providing an overall lower profile to the system. Thethinner wall and lower profile allows for a smaller insertion holethrough the vessel without impacting overall lumen size. In someimplementations, the wall thickness of the guide sheath 400 can slowlystep down to be thinner towards a distal end of the sheath compared to aproximal end.

The system can include localized points of low clearance between theguide sheath 400 and the catheter 200 extending through it. Thelocalized points of low clearance can provide localized sealing betweenthe structures. In some implementations, the localized sealing can benear the distal end region of the guide sheath 400 and in others thelocalized sealing can be a distance away from the distal end of theguide sheath 400. The catheter 200 can have an increase in OD near aproximal end region creating a cylindrical region of the catheter thatforms a snug fit (e.g. less than about 0.002″ clearance) with the ID ofthe guide sheath 400. The length of this low clearance sealing regioncan vary and depend on the overall clearance between the ID and OD.Greater differences in ID/OD (i.e. higher clearance) can providesufficient sealing at aspirational pressures by increasing the length ofthe cylindrical sealing region. Smaller differences in ID/OD (i.e. lowerclearance) can provide sufficient sealing at aspirational pressureswhile having a shorter cylindrical length. In other words, a shortersealing zone may have a closer fit or lower clearance whereas a longersealing zone need not have such a close fit and can have a higherclearance.

The guide sheath 400 can also include additional localized sealingpoints with the catheter extending through its working lumen. In someimplementations, the localized sealing can occur a distance away fromthe distal end 406 of the sheath 400. In some implementations, alocalized sealing can occur at the distal end 406 of the sheath 400. Forexample, the guide sheath 400 may include a distal tip 406 that isdesigned to seal well with an outer diameter of a catheter extendingthrough its working lumen. The distal tip 406 can be formed of softmaterial that is devoid of both liner and reinforcement layers. Thelubricious liner layer and also the reinforcement layer can extendthrough a majority of the body 402 except for a length of the distal tip406 (see FIG. 2C). The length of this unlined, unreinforced portion ofthe distal tip 406 of the sheath 400 can vary. In some implementations,the length is between about 3 mm to about 6 mm of the distal end regionof the sheath 400. Thus, the liner 409 of the sheath 400 can terminateat least about 3 mm away from the distal-most terminus of the sheath 400leaving the last 3 mm unlined soft material forming the distal tip 406.In some implementations, the coil and braid of the reinforcement layercan have their ends held in place by a radiopaque markers 411, such as amarker band positioned near a distal-most terminus of the sheath 400.The liner layer 409 can extend at least a length distal to the markerband 411 before terminating, for example, a length of about 1 mm. Thestaggered termination of the wall layers can aid in the transition fromthe marker band 411 to the soft polymer material 407 of the distal tip406. The soft polymer material 407 can extend a length beyond the linerlayer 409. The unlined, soft material 407 forming the distal tip 406 canbe a PEBAX material having a durometer of no more than about 40D, nomore than about 35D, no more than about 62A, or no more than about 25D.The softness of the material and the length of this unlined distal tip406 of the sheath 400 can vary. Generally, the material is soft enoughto be compressed down onto the outer diameter of the catheter 200extending through the lumen of the sheath 400, such as upon applicationof a negative pressure through the lumen. The length of this unlined,unreinforced region 407 of the distal tip 406 is long enough to providea good seal, but not so long as to cause problems with accordioning orfolding over during relative sliding between the sheath 400 and thecatheter 200 that might blocking the sheath lumen or negativelyimpacting slidability of the catheter 200 within the sheath lumen.

The distal tip 406 can have an inner diameter that approaches the outerdiameter of the catheter 200 that extends through the sheath 400. Insome implementations, the inner diameter of the distal tip 406 can varydepending on what size catheter is to be used. For example, the innerdiameter of the sheath at the distal tip 406 can be about 0.106″ whenthe outer diameter of the catheter near the proximal end is about 0.101″such that the difference in diameters is about 0.005″. Upon applicationof a vacuum, the soft unlined and unreinforced distal tip 406 can moveto eliminate this 0.005″ gap and compress down onto the outer diameterof the catheter 200 near its proximal end region upon extension of thecatheter 200 out its distal opening 408. The difference between theinner diameter of the distal tip 406 and the outer diameter of thecatheter can be between about 0.002″-0.006″. The inner diameter of thedistal tip 406 can also be tapered such the inner diameter at thedistal-most terminus of the opening 408 is only 0.001″ to 0.002″ largerthan the outer diameter of the proximal end of the catheter 200extending through the working lumen. In some implementations, the distaltip 406 is shaped such that the walls are beveled at an angle relativeto a central axis of the sheath 400, such as about 60 degrees.

In some instances it is desirable for the sheath body 402 to also beable to occlude the artery in which it is positioned, for example,during procedures that may create distal emboli. Occluding the arterystops antegrade blood flow and thereby reduces the risk of distal embolithat may lead to neurologic symptoms such as TIA or stroke. FIG. 2Dshows an arterial access device or sheath 400 that has a distalocclusion balloon 440 that upon inflation occludes the artery at theposition of the sheath distal tip 406. At any point in a procedure, forexample, during removal of an occlusion by aspiration and/or delivery ofa stent retriever or other interventional device, the occlusion balloon440 can be inflated to occlude the vessel to reduce the risk of distalemboli to cerebral vessels. The sheath 400 can include an inflationlumen configured to deliver a fluid for inflation of the occlusionballoon 440 in addition to the working lumen of the sheath 400. Theinflation lumen can fluidly connect the balloon 440, for example, to arm412 on the proximal adaptor. This arm 412 can be attached to aninflation device such as a syringe to inflate the balloon 440 with afluid when vascular occlusion is desired. The arm 412 may be connectedto a passive or active aspiration source to further reduce the risk ofdistal emboli.

According to some implementations, the length of the guide sheath 400 islong enough to access the target anatomy and exit the arterial accesssite with extra length outside of a patient's body for adjustments. Forexample, the guide sheath 400 (whether having a distal occlusion balloon440 or not) can be long enough to access the petrous ICA from thefemoral artery such that an extra length is still available foradjustment.

The sealing clearance between the guide sheath 400 and the catheter 200can be a function of localized low clearance regions in ID/OD. The sizeof the clearance can change depending on whether aspiration pressure isapplied through the system. For example, the catheter 200 can alsoinclude a slit 236 in the luminal portion 222 (shown in FIG. 5B)configured to widen slightly upon application of suction from anaspiration source and improve sealing between the catheter 200 and theguide sheath 400. Additionally or alternatively, the distal tip 406 ofthe sheath 400 can be designed to move downward onto the outer diameterof the catheter 200 to improve sealing. The strength of the localizedseal(s) achieved allows for a continuous aspiration lumen from thedistal tip of the catheter 200 to a proximal end 403 of the guide sheath400 where it is connected to the aspiration source, even in the presenceof lower suction forces, with minimal to no leakage. Generally, whenthere is enough overlap between the catheter 200 and the guide sheath400 there is no substantial leakage. However, when trying to reachdistal anatomy, the catheter 200 may be advanced to its limit and theoverlap between the catheter 200 and the guide sheath 400 is minimal.Thus, additional sealing can be desirable to prevent leakage around thecatheter 200 into the sheath 400. The sealing between the catheter 200and the guide sheath 400 can prevent this leakage upon maximal extensionof catheter 200 relative to sheath 400.

Distal Access Catheters

Again with respect to FIGS. 2A-2B, the distal access system 100 caninclude one or more catheters 200 configured to extend through and outthe distal end of the guide sheath 400. The catheter 200 can be a distalaccess, support, or aspiration catheter depending on the method beingperformed. FIG. 3 illustrates a side elevational view of animplementation of the catheter 200. The catheter 200 can include arelatively flexible, distal luminal portion 222 coupled to a stiffer,kink-resistant proximal extension or proximal control element 230. Theterm “control element” as used herein can refer to a proximal regionconfigured for a user to cause pushing movement in a distal direction aswell as pulling movement in a proximal direction. The control elementsdescribed herein may also be referred to as spines, tethers, push wires,push tubes, or other elements having any of a variety of configurations.The proximal control element can be a hollow or tubular element. Theproximal control element can also be solid and have no inner lumen, suchas a solid rod, ribbon or other solid wire type element. Generally, theproximal control elements described herein are configured to move itsrespective component (to which it may be attached or integral) in abidirectional manner through a lumen.

The catheter 200 provides a quick way to access stroke locations withsimplicity even through the extreme tortuosity of the cerebralvasculature. The catheters described herein have a degree of flexibilityand deliverability that makes them optimally suitable to be advancedthrough the cerebral vascular anatomy without kinking or ovalizing evenwhen navigating hairpin turns. For example, the distal luminal portion222 can perform a 180 degree turn (see turn T shown in FIG. 1B near thecarotid siphon) and maintain a folded width across of 4.0 mm withoutkinking or ovalizing. Further, the distal luminal portion 222 has adegree of flexibility that maintains the natural tortuosity of thevessels through which it is advanced without applying straighteningforces such that the natural shape and curvature of the anatomy ismaintained during use. The catheter 200, particularly in combinationwith a catheter advancement element 300, which will be described in moredetail below, provides an extended conduit beyond the guide sheath 400having exceptional deliverability through convoluted anatomy that allowsfor delivering aspirational forces to a target stroke site as well asfor the delivery of stroke interventional devices such as anotheraspiration catheter, or a device such as a stent retriever, stent, flowdiverter or other working devices.

A single, inner lumen 223 extends through the luminal portion 222between a proximal end and a distal end of the luminal portion 222. Theinner lumen 223 of the catheter 200 can have a first inner diameter andthe working lumen of the guide sheath 400 can have a second, largerinner diameter. Upon insertion of the catheter 200 through the workinglumen of the sheath 400, the lumen 223 of the catheter 200 can beconfigured to be fluidly connected and contiguous with the working lumenof the sheath 400 such that fluid flow into and/or out of the system 100is possible, such as by applying suction from an aspiration sourcecoupled to the system 100 at a proximal end. The combination of sheath400 and catheter 200 can be continuously in communication with thebloodstream during aspiration at the proximal end with advancement andwithdrawal of catheter 200.

The spined catheter system can create advantages for distal access overconventional, full-length catheters particularly in terms of aspiration.The step change in the internal diameter of the catheter (i.e. from theinner lumen 223 of the catheter to the working lumen of the sheath 400)creates a great advantage in aspiration flow and force that can begenerated by the spined catheter 200 in combination with theconventional guide catheter. For example, where a spined catheter 200with a 0.070″ internal diameter is paired with a standard 6F outerdiameter/0.088″ internal diameter guide catheter (e.g. Penumbra NeuronMAX 088) can create aspiration physics where the 0.088″ catheterdiameter will predominate and create a 0.080 equivalent flow in theentire system.

In addition to aspiration procedures, the catheter 200 and distal accesssystem 100 can be used for delivery of tools and interventional workingdevices. For example, a typical stent retriever to be delivered throughthe catheter 200 can have a long push wire control element (e.g. 180 cmlong). The distal access system 100 having a spined support catheter 200allows for reaching distal stroke sites using much shorter lengths (e.g.120 cm-150 cm). The overall length can be as important as diameter andradius on aspiration through the catheter. The shorter lengths incombination with the elimination of the multiple RHVs typical intri-axial systems allows for a single-operator use.

Where the catheter is described herein as an aspiration catheter itshould not be limited to only aspiration. Similarly, where the catheteris described herein as a way to deliver a stent retriever or otherworking device it should not be limited as such. The systems describedherein can be used to perform procedures that incorporate a combinationof treatments. For example, the catheter 200 can be used for thedelivery of a stent retriever delivery system, optionally in thepresence of aspiration through the catheter 200. As another example, auser may start out performing a first interventional procedure using thesystems described herein, such as aspiration embolectomy (sometimesreferred to as “thrombectomy”), and switch to another interventionalprocedure, such as delivery of a stent retriever or implant.

The terms “support catheter,” “spined catheter,” “tethered catheter,”“distal access catheter,” “aspiration catheter,” and “intermediatecatheter” may be used interchangeably herein.

It is desirable to have a catheter 200 having an inner diameter that isas large as possible that can be navigated safely to the site of theocclusion, in order to optimize the aspiration force in the case ofaspiration and/or provide ample clearance for delivery of a workingdevice. A suitable size for the inner diameter of the distal luminalportion 222 may range between 0.040″ and 0.100″, or more preferablybetween 0.054″ and 0.088″, depending on the patient anatomy and the clotsize and composition. The outer diameter of the distal luminal portion222 can be sized for navigation into cerebral arteries, for example, atthe level of the M1 segment or M2 segment of the cerebral vessels. Theouter diameter (OD) should be as small as possible while stillmaintaining the mechanical integrity of the catheter 200. In animplementation, the difference between the OD of distal luminal portion222 of the catheter 200 and the inner diameter of the working lumen ofthe guide sheath 400 is between 0.001″ and 0.002″. In anotherimplementation, the difference is between 0.001″ and 0.004″. Theclearance between inner diameter of the guide sheath 400 and the outerdiameter of the catheter 200 can vary throughout the length of thecatheter 200. For example, the distal luminal portion 222 of thecatheter 200 can have localized regions of enlarged outer diametercreating localized low clearance regions (e.g. about 0.001″ difference)configured for localized sealing upon application of aspiration pressurethrough the system.

In some implementations, the distal luminal portion 222 of the catheter200 has a maximum outer diameter (OD) configured to fit through a 6Fintroducer sheath (0.070″-0.071″) and the lumen 223 has an innerdiameter (ID) that is sized to receive a 0.054″ catheter. In someimplementations, the distal luminal portion 222 has a lumen and a distalend having an opening from the lumen, the lumen can have an innerdiameter (ID) at the distal end that is at least about 0.052″. In someimplementations, the distal luminal portion 222 of the catheter 200 hasa maximum OD configured to fit through an 8F introducer sheath (0.088″)and the lumen 223 has an ID that is sized to receive a 0.070″ or 0.071″catheter. In some implementations, the maximum OD of the distal luminalportion 222 is 2.1 mm and the lumen 223 has an ID that is 0.071″. Insome implementations, the lumen 223 has an ID that is 0.070″ to 0.073″.The outer diameter of the guide sheath 400 can be suitable for insertioninto at least the carotid artery, with a working lumen suitably sizedfor providing a passageway for the catheter 200 to treat an occlusiondistal to the carotid artery towards the brain. In some implementations,the ID of the working lumen can be about 0.074″ and the OD of the bodyof the guide sheath 400 can be about 0.090″, corresponding to a 5 Frenchsheath size. In some implementations, the ID of the working lumen can beabout 0.087″ and the OD of the body of the guide sheath 400 can be about0.104″, corresponding to a 6 French sheath size. In someimplementations, the ID of the working lumen can be about 0.100″ and theOD of the body of the guide sheath 400 can be about 0.117″,corresponding to a 7 French sheath size. In some implementations, theguide sheath 400 ID is between 0.087″ and 0.088″ and the OD of thedistal luminal portion 222 of the catheter 200 is approximately 0.082″and 0.086″ such that the difference in diameters is between 0.001″ and0.005″. Smaller or larger sheath sizes are considered. For example, insome implementations the ID of the lumen 223 is about 0.088″ and the ODof the distal luminal portion is between 0.101″-0.102″. However, aconventional 7 French sheath has an ID that is only about 0.100″ and aconventional 8 French sheath has an ID that is about 0.113″ such that itwould not provide a suitable sealing fit with the OD of the distalluminal portion of the catheter for aspiration embolectomy (i.e. 0.011″clearance). Thus, the guide sheath 400 can be designed to have an innerdiameter that is better suited for the 0.088″ catheter, namely between0.106″-0.107″. Additionally, the 0.088″ catheter can have a step-up inOD from 0.101″-0.102″ to about 0.105″-0.107″ OD near a proximal endregion to provide a localized area optimized for sealing with the guidesheath during application of high pressure.

In an implementation, the luminal portion 222 of the catheter 200 has auniform diameter from a proximal end to a distal end. In otherimplementations, the luminal portion 222 of the catheter 200 is taperedand/or has a step-down towards the distal end of the distal luminalportion 222 such that the distal-most end of the catheter 200 has asmaller outer diameter compared to a more proximal region of thecatheter 200, for example, near where the distal luminal portion 222seals with the guide sheath 400. In another implementation, the luminalportion 222 of the catheter OD steps up at or near an overlap portion tomore closely match the sheath inner diameter as will be described inmore detail below. This step-up in outer diameter can be due to varyingthe wall thickness of the catheter 200. For example, the catheter 200can have a wall thickness that is slightly thicker near the proximal endto provide better sealing with the sheath compared to a wall thicknessof the catheter 200 near the distal end. The catheter 200 can have athicker wall at this location while maintaining a uniform innerdiameter. This implementation is especially useful in a system with morethan one catheter suitable for use with a single access sheath size. Insome implementations, a thicker wall can be created by embedding aradiopaque material (e.g. tungsten) such that the localized step-up inOD can be visualized during a procedure. The catheter 200 may have astep-up in outer diameter near the proximal end region that does notresult from a thicker wall. For example, the inner diameter of the lumenmay also step-up such that the wall thickness remains uniform, but thelumen size increases thereby increasing the overall OD at this location.

The length of the luminal portion 222 can be shorter than a length ofthe working lumen of the guide sheath 400 such that upon advancement ofthe luminal portion 222 towards the target location results in anoverlap region 348 between the luminal portion 222 and the working lumen(see FIG. 2B). The length of the overlap region 348 can vary dependingon the length of the distal luminal portion 222 and the distance to thetarget location relative to the distal end of the guide sheath 400.Taking into account the variation in occlusion sites and sites where theguide sheath 400 distal tip 406 may be positioned, the length of theluminal portion 222 may range from about 10 cm to about 80 cm, orbetween 35 cm to about 75 cm, or between about 45 cm to about 60 cm. Insome implementations, the distal luminal portion 222 of the catheter 200can be between 45 cm-70 cm and the control element 230 of the catheter200 can be between about 90 cm to about 100 cm. In some implementations,the catheter 200 can have a total working length that is approximately115 cm. In other implementations, the working length of the catheter 200between a proximal end of the catheter to a distal end of the cathetercan be greater than 115 cm up to about 130 cm. In some implementations,the catheter 200 can have a working length greater than 130 cm between aproximal tab 234 (or proximal hub) and the distal tip, for example, 133cm. The distal luminal portion 222 can have a shaft length of about 40cm±3 cm. The distal luminal portion 222 can have a shaft length that isat least about 45 cm up to a length that is shorter than the workinglength of the sheath 400. The body 402 of the guide sheath 400 can bebetween about 80 cm to about 90 cm.

The length of the luminal portion 222 can be less than the length of thebody 402 of the guide sheath 400 such that as the catheter 200 isextended from the working lumen there remains an overlap region 348 ofthe catheter 200 and the inner diameter of the working lumen. A seal canbe formed within a region of the overlap region 348. In someimplementations, the length of the luminal portion 222 is sufficient toreach a region of the M1 segment of the middle cerebral artery (MCA) andother major vessels from a region of the internal carotid artery whilethe proximal end region of the luminal portion 222 of the catheter 200is still maintained proximal to certain tortuous anatomies (e.g.brachiocephalic take-off BT, the aortic arch AA, or within thedescending aorta DA). In an implementation, the luminal portion 222 ofthe catheter has a length sufficient to position its distal end withinthe M1 segment of the MCA and a proximal end within the aortic archproximal to take-offs from the arch. In an implementation, the luminalportion 222 of the catheter has a length sufficient to position itsdistal end within the M1 segment of the MCA and a proximal end withinthe descending aorta DA proximal to the aortic arch AA. Used inconjunction with a guide sheath 400 having a sheath body 402 and aworking lumen, in an implementation where the catheter 200 reaches theICA and the distance to embolus can be less than 20 cm.

The distal luminal portion 222 having a length that is less than 80 cm,for example approximately 45 cm up to about 70 cm, The distal luminalportion 222, can allow for an overlap region 348 with the body 402within which a seal forms with the sheath while still providingsufficient reach to intracranial vessels. The carotid siphon CS is anS-shaped part of the terminal ICA beginning at the posterior bend of thecavernous ICA and ending at the ICA bifurcation into the anteriorcerebral artery ACA and middle cerebral artery MCA. In someimplementations, the distal luminal portion 222 can be between about 35cm-80 cm, or between 40 cm-75 cm, or between 45 cm-60 cm long to allowfor the distal end of the catheter 200 to extend into at least themiddle cerebral arteries while the proximal control element 230 and/orthe sealing element on the proximal end region of the distal luminalportion 222 remains proximal to the carotid siphon, and preferablywithin the aorta as will be described in more detail below.

The distal luminal portion 222 can have a length measured from its pointof attachment to the proximal control element 230 to its distal end thatis long enough to extend from a region of the internal carotid artery(ICA) that is proximal to the carotid siphon to a region of the ICA thatis distal to the carotid siphon, including at least the M1 region of thebrain. There exists an overlap region 348 between the luminal portion222 of the catheter 200 and the working lumen of the guide sheath 400upon extension of the luminal portion 222 into the target anatomy. Aseal to fluid being injected or aspirated can be achieved within theoverlap region 348 where the OD of the catheter 200 along at least aportion of the distal luminal portion 222 substantially matches theinner diameter of the guide sheath 400 or the difference can be between0.001″-0.002″. The difference between the catheter OD and the innerdiameter of the guide sheath 400 can vary, for example, between 1-2thousandths of an inch, or between 1-4 thousandths of an inch, orbetween 1-12 thousandths of an inch. This difference in OD/ID betweenthe sheath and the catheter can be along the entire length of the distalluminal portion 222 or can be a difference in a discrete region of thedistal luminal portion 222, for example, a cylindrical, proximal endregion of the distal luminal portion 222. In some implementations, aseal to fluid being injected or aspirated between the catheter and thesheath can be achieved within the overlap 348 between theirsubstantially similar dimensions without incorporating any separatesealing structure or seal feature. In some implementations, anadditional sealing structure located near the proximal end region of thedistal luminal portion 222 provides sealing between the inner diameterof the sheath and the outer diameter of the catheter.

The length of the overlap region 348 between the sheath and the distalluminal portion varies depending on the distance between the distal endof the sheath and the embolus as well as the length of the luminalportion 222 between its proximal and distal ends. The overlap region 348can be sized and configured to create a seal that allows for acontinuous aspiration lumen from the distal tip region of the catheter200 to a proximal end region 403 of the guide sheath 400 where it can beconnected to an aspiration source. In some implementations, the strengthof the seal achieved can be a function of the difference between theouter diameter of the catheter 200 and the inner diameter of the workinglumen as well as the length of the overlap region 348, the force of thesuction applied, and the materials of the components. For example, thesealing can be improved by increasing the length of the overlap region348. However, increasing the length of the overlap region 348 can resultin a greater length through which aspiration is pulled through thesmaller diameter of the luminal portion 222 rather than the largerdiameter of the working lumen. As another example, higher suction forcesapplied by the aspiration source can create a stronger seal between theluminal portion 222 and the working lumen even in the presence of ashorter overlap region 348. Further, a relatively softer materialforming the luminal portion and/or the body 402 can still provide asufficient seal even if the suction forces are less and the overlapregion 348 is shorter. In an implementation, the clearance of theoverlap region 348 can enable sealing against a vacuum of up toapproximately 28 inHg with minimal to no leakage. The clearance of theoverlap region can enable sealing against a vacuum of up to about 730mmHg with minimal to no leakage.

In other implementations, the overlap region 348 itself does not providethe sealing between the body 402 and the luminal portion 222. Rather, anadditional sealing element positioned within the overlap region 348, forexample, a discreet location along a region of the luminal portion 222narrows the gap between their respective ID and ODs such that sealing isprovided by the sealing element within the overlap region 348. In thisimplementation, the location of the seal between the luminal portion 222and the body 402 can be positioned more proximally relative to certaintortuous regions of the anatomy. For example, the proximal end region ofthe luminal portion 222 can have a discreet step-up in outer diameterthat narrows the gap between the OD of the luminal portion 222 and theID of the body 402. This step-up in outer diameter of the luminalportion 222 can be positioned relative to the overall length of theluminal portion 222 such that the sealing region between the twocomponents avoids making sharp turns. For example, the sealing regioncan include the proximal end region of the luminal portion 222 a certaindistance away from the distal tip of the catheter and this sealingregion can be designed to remain within the descending aorta DA when thedistal end region of the luminal portion 222 is advanced through theaortic arch, into the brachiocephalic trunk BT, the right common carotidRCC, up to the level of the petrous portion of the internal carotidartery and beyond. Maintaining the sealing region below the level of theaortic arch while the distal end of the catheter is positioned within,for example, the M1 region of the MCA is a function of the length of theluminal portion 222 as well as the length and position of the sealingportion on the catheter. The sealing region on the luminal portion 222can be located a distance from the distal tip of the catheter that is atleast about 40 cm, 45 cm, 50 cm, 55 cm, 60 cm, 65 cm, 70 cm, up to about75 cm from the distal tip of the catheter.

Use of the term “seal” in the context of the catheter and the guidesheath refers to a condition where upon application of an aspirationforce fluid is prevented from substantially passing from one side of theseal to the other. For example, the low clearance between the OD of thecatheter and the ID of the sheath at the seal can prevent, uponapplication of aspiration pressure through the system, substantialpassage of blood between outer surface of the catheter and the innersurface of the sheath and thereby create a seal. The seal does notnecessarily mean the entire catheter system is sealed. For example, evenwhen the catheter is “sealed” with the sheath, blood can still beaspirated into the lumen of the catheter and through the guide sheath(at least until “corking” of the distal end of the catheter 200 where afull seal of the entire system may occur).

The catheter 200 can telescope relative to the sheath (and/or relativeto another catheter 200) such that the distal end of the distal luminalportion 222 can reach cerebrovascular targets within, for example, theM1, M2 regions while the proximal end of the distal luminal portion 222remains proximal to or below the level of severe turns along the path ofinsertion. For example, the entry location of the catheter system can bein the femoral artery and the target embolus can be distal to the rightcommon carotid artery (RCC), such as within the M1 segment of the middlecerebral artery on the right side. The proximal end region of the distalluminal portion 222 (e.g. where the sealing element is located and/orwhere the material transition to the proximal control element 230occurs) can remain within a vessel that is proximal to severely tortuousanatomy: the carotid siphon, the right common carotid RCC, thebrachiocephalic trunk BT, the take-off of the brachiocephalic arteryfrom the aortic arch, the aortic arch AA as it transitions from thedescending aorta DA. The descending aorta DA is a consistently straightsegment in most anatomies. FIG. 1C illustrates the aortic arch AA, whichseparates the ascending aorta AscA and descending aorta DA. Thedistal-most carotid from a femoral access point is the right commoncarotid RCC artery, which takes off from the brachiocephalic trunk BT(or the left common carotid LCC, which takes off from the samebrachiocephalic trunk BT in some patients—the so-called “bovineanatomy”). The distal luminal portion 222 may have a length that, wheninserted into the RCC, is configured to extend from a target location inthe M1 or M2 regions down to the brachiocephalic trunk BT, or down tothe level of the aortic arch AA, or down to the descending aorta DA,which is sometimes referred to herein as being “below the takeoff” ofthe brachiocephalic trunk BT. This avoids inserting the stiffer proximalcontrol element 230, or the material transition between the stifferproximal control element 230 and the distal luminal portion 222, fromtaking the turn of the aortic arch or the turn of the brachiocephalictake-off, which can often be very severe. The turn of the aortic archand the takeoff of the brachiocephalic are often the first severe turnscatheters are likely to traverse as they ascend to the brain via the RCCartery. The less flexible portions of the catheter segment are able toavoid the regions of increased tortuosity near the level of the internalcarotid artery. The distal luminal portion 222 can transition inflexibility towards the proximal region to approach the flexibility ofthe stiffer proximal control element 230. The distal end of the cathetercan be used to target the left cerebral circulation while the proximalcontrol element 230 of the catheter 200 as well as the materialtransitions of the distal luminal portion 222 near the proximal controlelement 230 remain below the level of tortuosity of the brachiocephalicturn (e.g., within the aorta, proximal to the take-off of the leftcommon carotid (LCC) artery, and preferably within the descending aortaDA). Similarly, the sealing region or a majority of the sealing regionbetween the distal luminal portion 222 and the sheath preferably remainsproximal to these severe turns.

In some implementations, the distal luminal portion 222 can have alength that allows the distal end of the distal luminal portion 222 toreach distal to the carotid siphon into the cerebral portion of theinternal carotid artery while at the same time the proximal end of thedistal luminal portion 222 (e.g. where it transitions to the proximalcontrol element 230 as will be described in more detail below) remainswithin the aorta proximal to the take-off of the brachiocephalic trunkBT, for example within the descending aorta DA (see FIG. 2C). In thisimplementation, the distal luminal portion can be between about 35 cmand 75 cm in length, for example, between 45 cm-70 cm, or 65 cm long.

The attachment region between the more rigid, proximal control element230 and the more flexible, distal luminal portion 222 creates atransition in material and flexibility that can be prone to kinking.Thus, it is preferable to avoid advancing the attachment region intoextreme curvatures. For example, the distal luminal portion 222 can havea length that allows the point of attachment to be advanced no furtherthan the first turn of the carotid siphon, or no further than thebrachiocephalic artery take-off 610, or nor further than the aortic archAA, or no further than the descending aorta DA when the catheter isadvanced from a femoral access site. In some implementations, the distalluminal portion 222 has a length sufficient to allow the point ofattachment to remain within the descending aorta DA while stillaccessing M1 or M2 regions of the neurovasculature. Locating thematerial transition within the extreme turn of the brachiocephalictake-off BT from the aortic arch AA is generally avoided when the distalluminal portion 222 has a length that is between about 35 cm to about 75cm, or 45 cm-70 cm, or 65 cm.

A seal can be created at and/or within the overlap region 348 betweenthe distal luminal portion 222 and the sheath body 402. It can begenerally desirable to position the sealing between the distal luminalportion 222 and the sheath body 402 outside of extreme curvatures of theneurovasculature. In some implementations, the distal luminal portion222 can have a length that allows for the distal end of the distalluminal portion 222 to extend distal to the carotid siphon into thecerebral portion of the internal carotid artery while at the same timethe sealing region with the sheath body 402 remains proximal to thebrachiocephalic takeoff BT, the aortic arch AA, or within the descendingaorta DA. In this implementation, the length can be between about 35 cmto about 75 cm, about 40 cm to about 65 cm, or greater than 40 cm up toa length that is less than the working length of the sheath body 402.

With respect to FIG. 2C, the unreinforced region 407 of the distal tip406 of the sheath 400 can have a length that allows it to providesufficient sealing force onto the outer surface of the catheter 200 uponapplication of a negative pressure. The distal luminal portion 222 ofthe catheter 200 used with this implementation of sheath 400 can have alength that is shorter than 60 cm, shorter than 50 cm, shorter than 40cm, shorter than 35 cm, shorter than 30 cm to about 10 cm. For example,the distal luminal portion 222 of the catheter 200 when used with asheath 400 having an unreinforced region 407 configured for sealingagainst the outer diameter of the catheter 200 can be less than about 30cm, for example, between about 10 cm and about 30 cm.

Sealing within the overlap region 348 can be due to the small differencein inner and outer diameters. The proximal end region of the distalluminal portion 222 can have a step-up in outer diameter (e.g. increasedwall thickness) providing a region of localized sealing with the innerdiameter of the guide sheath. Additionally or alternatively, thelocalized sealing can be due to an additional sealing element positionedon an external surface of the distal luminal portion or an inner surfaceof the sheath body. A sealing element can include a stepped up diameteror protruding feature in the overlap region. The sealing element caninclude one or more external ridge features. The one or more ridgefeatures can be compressible when the luminal portion is inserted intothe lumen of the sheath body. The ridge geometry can be such that thesealing element behaves as an O-ring, quad ring, or other piston sealdesign. The sealing element can include one or more inclined surfacesbiased against an inner surface of the sheath body lumen. The sealingelement can include one or more expandable members actuated to seal. Theinflatable or expandable member can be a balloon or covered braidstructure that can be inflated or expanded and provide sealing betweenthe two devices at any time, including after the catheter is positionedat the desired site. Thus, no sealing force need be exerted on thecatheter during positioning, but rather applied or actuated to sealafter the catheter is positioned. The sealing element can be positionedon the external surface of the distal luminal portion, for example, nearthe proximal end region of the distal luminal portion and may be locatedwithin the overlap region. More than a single sealing element can bepositioned on a length of the catheter.

The additional sealing element of the distal luminal portion 222 can bea cup seal, a balloon seal, or a disc seal formed of a soft polymerpositioned around the exterior of the distal luminal portion near theoverlap region to provide additional sealing. The sealing element can bea thin-wall tubing with an outer diameter that substantially matches theinner diameter of the sheath body lumen. The tubing can be sealed on oneend to create a cup seal or on both ends to create a disc or balloonseal. The balloon seal can include trapped air that creates acollapsible space. One or more slits can be formed through the walltubing such that the balloon seal can be collapsible and more easilypassed through an RHV. The balloon seal need not include slits for aless collapsible sealing element that maintains the trapped air. Thesealing element can be tunable for sheath fit and collapse achieved.

In some implementations, the system can include one or more featuresthat restrict extension of the catheter 200 relative to the sheath 400to a particular distance such that the overlap region 348 achieved isoptimum and/or the catheter 200 is prevented from being over-inserted.For example, a tab can be positioned on a region of the catheter 200such that upon insertion of the catheter 200 through the sheath 400 aselected distance, the tab has a size configured to abut against theport through which the catheter 200 is inserted to prevent furtherdistal extension of the catheter 200 through the sheath 400. A tab canalso be positioned on a region of the catheter advancement element 300to ensure optimum extension of the catheter advancement element 300relative to the distal end of the catheter 200 to aid in advancement ofthe catheter 200 into the intracranial vessels.

Again with respect to FIG. 3, the proximal control element 230 isconfigured to move the distal luminal portion 222 in a bidirectionalmanner through the working lumen of the guide sheath 400 such that thedistal luminal portion 222 can be advanced out of the guide sheath 400into a target location for treatment within the target vessel. In someimplementations and as shown in FIG. 3, the proximal control element 230of the catheter 200 can have a smaller outer diameter than the outerdiameter of the distal luminal portion 222 forming a proximal spine ortether to the catheter 200. A smaller outer diameter for the proximalcontrol element 230 than the outer diameter of the distal luminalportion 222 allows for the larger diameter working lumen of the sheath400 to maintain greater aspiration forces than would otherwise beprovided by the smaller diameter luminal portion 222 of the catheter 200or allow for the delivery of working devices through the lumen with lessfrictional forces. The markedly shorter length of the luminal portion222 results in a step-up in luminal diameter between the luminal portion222 contiguous with the working lumen providing a markedly increasedradius and luminal area for delivery of a working device and/oraspiration of the clot, particularly in comparison to other systemswhere the aspiration lumen runs along the entire inner diameter of theaspiration catheter. More particularly, the combined volume of theluminal area of the catheter 200 and the luminal area of the workinglumen proximal to the distal luminal portion 222 is greater than theluminal area of the large bore catheter along the entire length of thesystem. Thus, the likelihood of removing the embolus during a singleaspiration attempt may be increased. More particularly, the stepped upluminal diameter along the proximal control element 230 may enable agreater aspiration force to be achieved resulting in improved aspirationof the embolus. Further, this configuration of the catheter 200 andproximal control element 230 greatly speeds up the time required toretract and re-advance the catheter 200 and/or working devices throughthe working lumen out the distal opening 408. The proximal controlelement 230 of the catheter 200 has a length and structure that extendsthrough the working lumen of the sheath-guide 400 to a proximal end ofthe system 100 such that the proximal control element 230 can be used toadvance and retract the catheter 200 through the working lumen. Theproximal control element 230 of the catheter 200, however, takes up onlya fraction of the luminal space of the system 100 resulting in increasedluminal area for aspiration and/or delivery of working devices. Thestepped up luminal diameter also increases the annular area availablefor forward flushing of contrast, saline, or other solutions whiledevices such as microcatheters or other devices may be coaxiallypositioned in the luminal portion 222 of the catheter 200 and/or theworking lumen. This can increase the ease and ability to performangiograms during device navigation.

In an implementation, the distal luminal portion 222 of the catheter 200is constructed to be flexible and lubricious, so as to be able to safelynavigate to the target location. The distal luminal portion 222 can bekink resistant and collapse resistant when subjected to high aspirationforces so as to be able to effectively aspirate a clot. The luminalportion 222 can have increasing flexibility towards the distal end withsmooth material transitions along its length to prevent any kinks,angulations or sharp bends in its structure, for example, duringnavigation of severe angulations such as those having 90° or greater to180° turns, for example at the aorto-iliac junction, the left subclavianartery LSA take-off from the aorta AA, the takeoff of thebrachiocephalic (innominate) artery BT from the ascending aorta AscA andmany other peripheral locations just as in the carotid siphon. Thedistal luminal portion 222 can transition from being less flexible nearits junction with the proximal control element 230 to being moreflexible at the distal-most end. For example, a first portion of thedistal luminal portion 222 can be formed of a material having a materialhardness of 72D along a first length, a second portion can be formed ofa material having a material hardness of 55D along a second length, athird portion can be formed of a material such as Pebax or MX1205 havinga material hardness of 40D along a third length, a fourth portion can beformed of a material having a material hardness of 35D along a fourthlength, a fifth portion can be formed of a material having a materialhardness of 25D along a fifth length, a sixth portion can be formed of amaterial such as Tecoflex having a material hardness of 85A along asixth length, and a final distal portion of the catheter can be formedof a material such as Tecoflex having a material hardness of 80A. Insome implementations, the final distal portion of the distal luminalportion 222 of the catheter 200 can be formed of a material such asTecothane having a material hardness of 62A. Thus, the distal luminalportion 222 transitions from being less flexible near its junction withthe proximal control element 230 to being more flexible at thedistal-most end where, for example, a distal tip of the catheteradvancement element 300 can extend from the distal end of the catheter200. Other procedural catheters described herein can have a similarconstruction providing a variable relative stiffness that transitionsfrom the proximal end towards the distal end of the catheter as will bedescribed elsewhere herein. The change in flexibility from proximal todistal end of the distal luminal portion 222 can be achieved by any of avariety of methods.

The distal luminal portion 222 can include two or more layers. In someimplementations, the distal luminal portion 222 includes an innerlubricious liner, a reinforcement layer, and an outer jacket layer, eachof which will be described in more detail.

The lubricious inner liner can be a PTFE liner, with one or morethicknesses along variable sections of flexibility. The PTFE liner canbe a tubular liner formed by dip coating or film-casting a removablemandrel, such as a silver-plated copper wire as is known in the art.Various layers can be applied having different thicknesses. For example,a base layer of etched PTFE can be formed having a thickness of about0.005″. A second, middle layer can be formed over the base layer that isTecoflex SG-80A having a thickness of about 0.0004″. A third, top layercan be formed over the middle layer that is Tecoflex SG-93A having athickness of about 0.0001″ or less. A reinforcement layer and/orreinforcement fiber can be applied to the inner liner, followed by theouter jacket layer and/or additional outer coating prior to removing themandrel by axial elongation.

The reinforcement layer is a generally tubular structure formed of, forexample, a wound ribbon or wire coil or braid. The material for thereinforcement structure may be stainless steel, for example 304stainless steel, Nitinol, cobalt chromium alloy, or other metal alloythat provides the desired combination of strengths, flexibility, andresistance to crush. In some implementations, the distal luminal portion222 has a reinforcement structure that is a Nitinol ribbon wrapped intoa coil. For example, the coil reinforcement can be a tapered ribbon ofNitinol set to a particular inner diameter (e.g. 0.078″ to 0.085″ innerdiameter) and having a pitch (e.g. between 0.012″ and 0.016″). Theribbon can be 304 stainless steel (e.g. about 0.012″×0.020″). The coilcan be heat-set prior to transferring the coil onto the catheter. Thepitch of the coil can increase from proximal end towards distal end ofthe distal luminal portion 222. For example, the ribbon coils can havegaps in between them and the size of the gaps can increase movingtowards the distal end of the distal luminal portion 222. For example,the size of the gap between the ribbon coils can be approximately 0.016″gap near the proximal end of the distal luminal portion 222 and the sizeof the gap between the ribbon coils near the distal end can be largersuch as 0.036″ gap. This change in pitch provides for increasingflexibility near the distal-most end of the distal luminal portion 222.The distal luminal portion 222 can additionally incorporate one or morereinforcement fibers (see FIGS. 8B-8C) configured to prevent elongationof the coils, as will be described in more detail below. Thereinforcement structure can include multiple materials and/or designs,again to vary the flexibility along the length of the distal luminalportion 222.

The outer jacket layer may be composed of discreet sections of polymerwith different durometers, composition, and/or thickness to vary theflexibility along the length of the distal luminal portion 222.

At least a portion of the outer surface of the catheter 200 can becoated with a lubricious coating such as a hydrophilic coating. In someimplementations, the coating may be on an inner surface and/or an outersurface to reduce friction during tracking. The coating may include avariety of materials as is known in the art. The proximal controlelement 230 may also be coated to improve tracking through the workinglumen. Suitable lubricious polymers are well known in the art and mayinclude silicone and the like, hydrophilic polymers such as high-densitypolyethylene (HDPE), polytetrafluoroethylene (PTFE), polyarylene oxides,polyvinylpyrolidones, polyvinyl alcohols, hydroxy alkyl cellulosics,algins, saccharides, caprolactones, HYDAK coatings (e.g. B-23K,HydroSleek), and the like, and mixtures and combinations thereof.Hydrophilic polymers may be blended among themselves or with formulatedamounts of water insoluble compounds (including some polymers) to yieldcoatings with suitable lubricity, bonding, and solubility.

In some implementations, the distal luminal portion 222 includes two ormore layers. In some implementations, the distal luminal portion 222includes an inner lubricious liner, a reinforcement layer, and an outerjacket layer. The outer jacket layer may be composed of discreetsections of polymer with different durometers, composition, and/orthickness to vary the flexibility along the length of the distal luminalportion 222. In an implementation, the lubricious inner liner is a PTFEliner, with one or more thicknesses along variable sections offlexibility. In an implementation, the reinforcement layer is agenerally tubular structure formed of, for example, a wound ribbon orwire coil or braid. The material for the reinforcement structure may bestainless steel, for example 304 stainless steel, nitinol, cobaltchromium alloy, or other metal alloy that provides the desiredcombination of strengths, flexibility, and resistance to crush. In animplementation, the reinforcement structure includes multiple materialsand/or designs, again to vary the flexibility along the length of thedistal luminal portion 222. In an implementation, the outer surface ofthe catheter 200 is coated with a lubricious coating such as ahydrophilic coating. The proximal control element 230 may also be coatedto improve tracking through the working lumen. Suitable lubriciouspolymers are well known in the art and may include silicone and thelike, hydrophilic polymers such as high-density polyethylene (HDPE),polytetrafluoroethylene (PTFE), polyarylene oxides,polyvinylpyrolidones, polyvinyl alcohols, hydroxy alkyl cellulosics,algins, saccharides, caprolactones, and the like, and mixtures andcombinations thereof.

Again with respect to FIGS. 2A-2B, the distal luminal portion 222 of thecatheter 200 can have a plurality of radiopaque markings. A firstradiopaque marker 224 a can be located near the distal tip region to aidin navigation and proper positioning of the tip under fluoroscopy.Additionally, a proximal region of the catheter 200 may have one or moreproximal radiopaque markers 224 b so that the overlap region 348 can bevisualized as the relationship between a radiopaque marker 411 on theguide sheath 400 and the radiopaque marker 224 b on the catheter 200.The proximal region of the catheter 200 may also have one or moreradiopaque markings providing visualization, for example, of theproximal opening into the single lumen of the catheter as will bedescribed in more detail below. In an implementation, the two radiopaquemarkers (marker 224 a at distal tip and a more proximal marker 224 b)are distinct so as to minimize confusion of the fluoroscopic image, forexample the catheter proximal marker 224 b may be a single band and themarker 411 on the guide sheath 400 may be a double band and any markerson a working device delivered through the distal access system can haveanother type of band or mark. The radiopaque markers 224 of the distalluminal portion 222, particularly those near the distal tip regionnavigating extremely tortuous anatomy, can be relatively flexible suchthat they do not affect the overall flexibility of the distal luminalportion 222 near the distal tip region. The radiopaque markers 224 canbe tungsten-loaded or platinum-loaded markers that are relativelyflexible compared to other types of radiopaque markers used in deviceswhere flexibility is not paramount. In some implementations, theradiopaque marker can be a band of tungsten-loaded PEBAX having adurometer of 35D.

As best shown in FIGS. 8B-8C, at least one reinforcement fiber 801 canbe incorporated within a wall of the distal luminal portion 222 toprevent elongation of a coiled reinforcement layer 803. The fiber 801can be positioned between the liner layer 805 and the reinforcementlayer 803. The fiber 801 can extend along the longitudinal axis A of thecatheter 200 from a proximal end region of the distal luminal portion222 to a distal end region of the portion 222. The proximal end of thefiber 801 can be coupled to a region of the distal luminal portion 222near where it couples to the proximal control element 230. A distal endof the fiber 801 can terminate near the distal end of the distal luminalportion 222. The distal end of the fiber 801 can be captured between thedistal marker band 224 a and an end of the reinforcement layer 803. Thedistal marker band 224 a can be fully encapsulated between the innerliner 805 and the outer jacket 807. In some implementations, the distalend of the fiber 801 extends distal to the last coil of thereinforcement layer 803 running under the marker band 224 a and thenlooping around the band 224 a back in a proximal direction. The free endof the fiber 801 is thereby captured under the reinforcement layer 803and the marker band 224 a. The reinforcement fiber 801 thus terminatesat the location the reinforcement layer 803 terminates thereby leaving alength of between about 10 cm-12 cm of the unreinforced distal-most tipregion. The catheter 200 can include a plurality of reinforcement fibers801 extending longitudinally along the distal luminal portion 222, suchas two, three, four, or more fibers 801 distributed around thecircumference of the portion 222 and aligned parallel with one anotherand with the longitudinal axis A of the catheter 200. The reinforcementfiber 801 may also terminate at a more distal location or at a moreproximal location than the location of the distal terminal marker 224 a.The material of the reinforcement fiber 801 can vary, including but notlimited to various high tenacity polymers like polyester, PEEK, andother similar materials.

The distal luminal portion 222 of the catheter 200 can have a proximalcontrol element 230 coupled near a proximal opening into the singlelumen of the distal luminal portion 222. The distal luminal portion 222and the proximal control element 230 can be attached to one another by acoupling band 901 (see FIGS. 9A-9C). A proximal end 905 of the couplingband 901 can attach to a distal end of the proximal control element 230and a distal end of the coupling band 901 can attach to the distalluminal portion 222. The proximal end 905 of the coupling band 901 mayinclude a slot 907 configured to be welded with the proximal controlelement 230 of the catheter 200. The catheter 200 may include a strainrelief along a skive length such as a tungsten loaded PEBAX. The distalend of the coupling band 901 can be cut to form a plurality of spirals903. These spirals 903 are configured to intersperse with the coils ofthe reinforcement layer 803 at the proximal end region of the distalluminal portion 222. The size of the gap between the spirals 903 of thecoupling band 901 can be substantially similar to the size of the gapbetween the coils of the reinforcement layer 803 such that they canneatly intersperse with one another without creating any localized areasof increased wall thickness due to overlap. The thickness of the spirals903 can, but need not, be similar to the thickness of the ribbon formingthe reinforcement layer 803. For example, the coiled reinforcement layer803 can be formed of a Nitinol ribbon having a thickness of about0.003″. The coupling band 901 can have a wall thickness that is about0.003″ such that the spirals 903 and the coils of the reinforcementlayer 803 can be similar in material thickness. This similarity inmaterial thickness between the coils and the spirals 903 contribute to agenerally uniform outer profile that can be kept to a minimum and avoidcreating a substantially increased wall thickness in this couplingregion. A low profile proximal end of the distal luminal portion 222aids in maximizing the inner diameter while keeping the outer diameteras small as possible, for example, such that the inner diameter of theguide sheath to a minimum (e.g. less than about 0.113″ or about 0.107″).The coupling band 901 can include an aperture 911 through middle region909 that is configured to receive a proximal end of the reinforcementfiber 801 extending longitudinally through the distal luminal portion222. The region of overlap between the distal end of the proximalcontrol element and the distal luminal portion 222 can vary, but can beat least about 5 mm, at least about 7 mm, at least about 10 mm toprovide a smooth and even transition. The overlap between the proximalcontrol element and the distal luminal portion 222 may be about 5 mm upto about 15 mm.

As mentioned the distal end of the proximal control element 230 can bewelded to the proximal end 905 of the coupling band 901. In someimplementations, the distal end region of the proximal control element230 is skived in places and is flat in other places. The proximalcontrol element 230 can be a stainless steel ribbon (e.g. 0.012″×0.020″or 0.014″×0.020″ along a majority of its length). A distal end region ofthe proximal control element 230 can have a discontinuous taper thatallows for the thickness of the ribbon to transition from the thicknessof 0.012″ or 0.014″ down to a thickness that matches or is notsignificantly different from a thickness of the spirals 903 on thecoupling band 901 that is attached to a proximal end region of thedistal luminal portion 222. The discontinuous taper can include a flatlength bound on proximal and distal ends by a tapered length. The flatlength allows for a more uniform, minimum material thickness between thedistal luminal portion 222 and the proximal control element 230 thatavoids introducing weak points that are more prone to kinking. Forexample, the distal end region of the proximal control element 230 canhave a first tapered length that transitions in thickness from 0.012″ toa thickness of 0.008″ and a second tapered length that transitions fromthe flat length thickness down to about 0.003″. In otherimplementations, the distal end region of the proximal control element230 can have a first tapered length that transitions in thickness from0.014″ to a thickness of 0.010″ and a second tapered length thattransitions from the flat length thickness down to about 0.003″. Thespirals 903 of the coupling band 901 can have a thickness matches thisterminal thickness of the proximal control element 230. The lengths ofthe tapered and flat portions can vary. In some implementations, thefirst tapered length can be approximately 0.12 cm, the flat length canbe approximately 0.2 cm, and the second tapered length can beapproximately 0.15 cm. The uniform thickness along this flat lengthprovides for a useful target in terms of manufacturing the catheter. Thecatheter need not incorporate a ribbon proximal control element 230 andcan have any of a variety of configuration as described elsewhereherein.

As mentioned previously, the proximal control element 230 is configuredto allow distal advancement and proximal retraction of the catheter 200through the working lumen of the guide sheath 400 including passage outthe distal opening 408. In an implementation, the length of the proximalcontrol element 230 is longer than the entire length of the guide sheath400 (from distal tip to proximal valve), such as by about 5 cm to 15 cm.The length of the body 402 can be in the range of 80 to 90 cm or up toabout 100 cm or up to about 105 cm and the length of the proximalcontrol element 230 can be between 90-100 cm.

Again with respect to FIG. 3, the proximal control element 230 caninclude one or more markers 232 to indicate the overlap between thedistal luminal portion 222 of the catheter 200 and the sheath body 402as well as the overlap between the distal luminal portion 222 of thecatheter 200 and other interventional devices that may extend throughthe distal luminal portion 222. At least a first mark 232 a can be anRHV proximity marker positioned so that when the mark 232 a is alignedwith the sheath proximal hemostasis valve 434 during insertion of thecatheter 200 through the guide sheath 400, the catheter 200 ispositioned at the distal-most position with the minimal overlap lengthneeded to create the seal between the catheter 200 and the workinglumen. At least a second mark 232 b can be a Fluoro-saver marker thatcan be positioned on the control element 230 and located a distance awayfrom the distal tip of the distal luminal portion 222. In someimplementations, a mark 232 can be positioned about 100 cm away from thedistal tip of the distal luminal portion 222.

The proximal control element 230 can include a gripping feature such asa tab 234 on the proximal end to make the proximal control element 230easy to grasp and advance or retract. The tab 234 can couple with one ormore other components of the system as will be described in more detailbelow. The proximal tab 234 can be designed to be easily identifiableamongst any other devices that may be inserted in the sheath proximalvalve 434, such as guidewires or retrievable stent device wires. Aportion of the proximal control element 230 and/or tab 234 can becolored a bright color, or marked with a bright color, to make it easilydistinguishable from guidewire, retrievable stent tethers, or the like.Where multiple catheters 200 are used together in a nesting fashion toreach more distal locations within the brain, each proximal controlelement 230 and/or tab 234 can be color-coded or otherwise labeled toclearly show to an operator which proximal control element 230 of whichcatheter 200 it is coupled to. The proximal portion 366 of the catheteradvancement element 300 can also include a color to distinguish it fromthe proximal control element 230 of the catheter 200.

The tab 234 can be integrated with or in addition to a proximal hubcoupled to a proximal end of the control element 230. For example, aswill be described in more detail below, the proximal control element 230can be a hypotube having a lumen. The lumen of the hypotube can be influid communication with the proximal hub at a proximal end of thecontrol element 230 such that aspiration forces and/or fluids can bedelivered through the hypotube via the proximal hub. The proximalcontrol element 230 can also be a solid element and need not include alumen to direct aspiration forces to the distal end of the catheter 200.

The proximal control element 230 can be configured with sufficientstiffness to allow advancement and retraction of the distal luminalportion 222 of the catheter 200, yet also be flexible enough to navigatethrough the cerebral anatomy as needed without kinking. Theconfiguration of the proximal control element 230 can vary. In someimplementations, the proximal control element 230 can be a tubularelement having an outer diameter that is substantially identical to theouter diameter of the distal luminal portion 222 similar to a typicalcatheter device. In other implementations, the outer diameter of theproximal control element 230 is sized to avoid taking up too muchluminal area in the lumen of the guide sheath 400 to provide a step-upin inner diameter for aspiration.

The proximal control element 230 can be a solid metal wire that isround, rectangular, trapezoid, D-shape, or oval cross-sectional shape(see FIGS. 4A-4G). The proximal control element 230 can be a flattenedribbon of wire having a rectangular cross-sectional shape as shown inFIG. 4A. The flattened ribbon of wire can also have square, rectangular,or other cross-sectional shape. The ribbon of wire can be curved into acircular, oval, c-shape, or quarter circle or other cross-sectional areaalong an arc. As such, an inner-facing surface of the ribbon can besubstantially flat and an outer-facing surface of the ribbon (i.e. thesurface configured to abut against an inner diameter of the accesssheath through which it extends) can be substantially curved (see FIGS.4F-4G). The curvature of the surface can substantially match thecurvature of the inner surface of the access sheath. The resultingcross-sectional shape of such a ribbon can be generally trapezoidal. Theoverall dimensions of the ribbon can vary depending on itscross-sectional shape and the size of the distal luminal portion. The0.054″ sized catheter 200 can have a proximal control element 230 thatis trapezoidal or D-shaped in cross-section. The inner-facing, flatsurface can have a width that is approximately 0.020″ wide and in thecase of the trapezoidal-shaped implementation, the outer-facing, curvedsurface can extend along an arc that is approximately 0.030″ long. The0.070″ sized catheter 200 can have a proximal extension that istrapezoidal or D-shaped in cross-section, and the width of theinner-facing, flat surface is slightly greater, for example,approximately 0.025″ and in the case of the trapezoidal-shapedimplementation, the outer-facing, curved surface can extend along an arcthat is approximately 0.040″ long. The 0.088″ sized catheter 200 canhave a proximal extension that is trapezoidal or D-shaped incross-section, and the width of the inner-facing, flat surface isapproximately 0.035″ and the outer-facing, curved surface of thetrapezoidal-shaped implementation can extend along an arc that isapproximately 0.050″ long.

The proximal control element 230 can be a hollow wire having a lumen 235extending through it, such as a hypotube as shown in FIG. 4B. Thehypotube can have an oval or circular shape. In an implementation, theproximal control element 230 is a ribbon of stainless steel havingdimensions of about 0.012″×0.020″. In an implementation, the proximalcontrol element 230 is a ribbon of stainless steel having dimensions ofabout 0.014″×0.020″. In an implementation, the proximal control element230 is a round wire, with dimensions from 0.014″ to 0.018″. In anotherimplementation, the proximal control element 230 is a ribbon withdimensions ranging from 0.010″ to 0.015″ thick, and 0.015″ thick to0.025″ thick. In an implementation, the proximal control element 230 isa hypotube formed from a flattened ribbon of stiff material rolled intoa tubular shape to have a lumen 235. In some implementations, theproximal control element 230 can be formed of a flattened ribbon ofstainless steel and rolled into a hypotube such that the proximalcontrol element 230 has a wall thickness of about 0.007″, an innerdiameter of about 0.004″ and an outer diameter of about 0.018″ beforethe hypotube is modified into an oval cross-sectional shape. Theovalized hypotube can maintain an inner diameter that is at least 0.001″along at least a first dimension and an outer diameter that is at least0.015″ along at least a first dimension. In an implementation, theproximal control element 230 material is a metal such as a stainlesssteel or nitinol as well as a plastic such as any of a variety ofpolymers.

In an implementation, the proximal control element 230 o is a stainlesssteel hypotube having an oval cross-sectional shape (see FIG. 4B). Theoval tubular shape can increase the column strength, pushability andkink resistance of the proximal control element 230 o for improvedadvancement through tortuous anatomy. The cross-sectional area of anoval hypotube minimizes the impact of the catheter 200 on movement ofother tools through the working lumen 410 of the sheath 400. FIG. 4Cillustrates a cross-sectional view of the working lumen 410 of thesheath 400 having a proximal control element 230 r extendingtherethrough. The proximal control element 230 r has a rectangularcross-sectional shape. FIG. 4D illustrates a cross-sectional view of theworking lumen 410 having an ovalized hypotube proximal control element230 o and a catheter advancement element 300 extending therethrough.FIG. 4E illustrates the comparison of surface area between therectangular-shaped ribbon and the oval hypotube. The oval hypotube 230 ohas less surface area compared to the rectangular-shaped ribbon 230 rallowing for a greater flow rate through the working lumen 410, forexample, during application of aspirating forces. The materials,dimensions, and shape of the proximal control element 230 can beselected based on the materials, dimensions, and shape of the distalluminal portion 222. For example, the proximal control element 230 canbe a rectangular ribbon of 340 stainless steel that is 0.012″×0.020″ andthe distal luminal portion 222 can have an inner diameter of about0.054″ to about 0.072″. In a further implementation, the proximalcontrol element 230 can be a rectangular ribbon of 340 stainless steelthat is 0.014″×0.020″ and the distal luminal portion 222 can have aninner diameter of about 0.088″. The additional heft of the stainlesssteel ribbon 230 can be useful in advancing a larger inner diametercatheter without kinking.

Now with respect to FIGS. 5A-5F, the junction between the distal luminalportion 222 of the catheter 200 and the proximal control element 230 canbe configured to allow a smooth transition of flexibility between thetwo portions so as not to create a kink or weak point. The smoothtransition at the joint between the distal luminal portion 222 and theproximal control element 230 also allows for smooth passage of devicesthrough the contiguous inner lumen created by the working lumen of theguide sheath 400 and the lumen 223 of the luminal portion 222 of thecatheter 200. In an implementation, the distal luminal portion 222 has atransition section 226 near the proximal opening into the single lumenand where the luminal portion 222 couples to the proximal controlelement 230 (see FIG. 5A). The transition section 226 can have an angledcut such that there is no abrupt step transition from the working lumenof the guide sheath 400 to the inner lumen 223 of the catheter 200. Theangled cut can be generally planer. In an alternate implementation, theangled cut is curved or stepped to provide a more gradual transitionzone. The proximal end region of the distal luminal portion 222 can beangled in an oblique manner relative to a longitudinal axis of thecatheter 200 such that the proximal end and proximal opening into thelumen are at an angle other than 90° to the longitudinal axis of thecatheter 200, for example between approximately 0°, 5°, 10°, 15°, 20°,25°, 30°, 35°, 40°, or 45° up to less than 90°. The proximal end regionof the distal luminal portion 222 can also be aligned substantiallyperpendicular to the longitudinal axis of the catheter 200 such that theproximal end and proximal opening into the lumen are substantially 90°to the longitudinal axis of the catheter 200. Similarly, the distal endregion of the distal luminal portion 222 can be angled in an obliquemanner relative to a longitudinal axis of the catheter 200 such that thedistal end and distal opening from the lumen 223 are at an angle otherthan 90° to the longitudinal axis of the catheter 200, for examplebetween approximately 0°, 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, or 45°up to less than 90°. The distal end region of the distal luminal portion222 can also be aligned substantially perpendicular to the longitudinalaxis of the catheter 200 such that the distal end and distal openinginto the lumen are substantially 90° to the longitudinal axis of thecatheter 200.

The proximal control element 230 can be coupled to a proximal end regionof the catheter 200 and/or may extend along at least a portion of thedistal luminal portion 222 such that the proximal control element 230couples to the distal luminal portion 222 a distance away from theproximal end defining the proximal opening into the lumen, for examplevia the coupling band 901. The proximal control element 230 can becoupled to the distal luminal portion 222 by a variety of mechanismsincluding bonding, welding, gluing, sandwiching, stringing, tethering,or tying one or more components making up the proximal control element230 and/or portion 222. The distal luminal portion 222 and the proximalcontrol element 230 may be joined by a weld bond, a mechanical bond, anadhesive bond, or some combination thereof. In some implementations, theproximal control element 230 and luminal portion 222 are coupledtogether by sandwiching the proximal control element 230 between layersof the distal luminal portion 222. For example, the proximal controlelement 230 can be a hypotube or rod having a distal end that is skived,ground or cut such that the distal end can be laminated or otherwiseattached to the layers of the catheter portion 222 near a proximal endregion. The skive length of the proximal control element 230 can beabout 7 mm and can incorporate a tungsten loaded Pebax strain reliefalong the length. The region of overlap between the distal end of theproximal control element 230 and the portion 222 can be at least about 1cm. This type of coupling allows for a smooth and even transition fromthe proximal control element 230 to the luminal portion 222.

Still with respect to FIGS. 5A-5F, the transition section 226 of thedistal luminal portion 222 can open up into a proximal tail 238extending a length proximal to the transition section 226. In someimplementations, the proximal tail 238 has a cross-sectional geometrythat is substantially curved. For example, the proximal tail 238 canextend along an arc of the longitudinal axis of the catheter 200 betweenabout 20 to about 90 degrees. In some implementations, the proximal tail238 is curved to create a funnel-shape and aids in loading and reloadinga catheter advancement element 300 into the lumen of the catheter 200.In other implementations, the edges of the proximal tail 238 curve suchthat the proximal tail 238 is not substantially flat. The curved shapecan vary including a tear-drop shape that allows for a smooth transitionand better loading/reloading of the catheter advancement element 300into the lumen and avoids flat edges that can abut and catch thecomponent as it is inserted. In other implementations, the proximal tail238 is substantially flat. The proximal tail 238 can provide a smoothtransition between distal luminal portion 222 and proximal controlelement 230 when the device is forced to bend. This can reduce thelikelihood of kinking and facilitate pushing against resistance.

The dimensions of the proximal tail 238 can vary. The proximal tail 238shown in FIGS. 5A-5F is relatively wide compared to the width of theproximal control element 230 and, in turn, can have a greater lengthwithout negatively impacting the ability of other devices to insertthrough the proximal opening into the lumen at the transition region226. In other implementations, the proximal tail 238, defined by aregion that is unsupported by the coils of the reinforcement layer 803and located proximal to the coupling band 901, can have a shorterlength. The width of this proximal tail 238 can taper along this shorterlength to a width of the proximal control element 230. The taperedshorter proximal tail 238 can mitigate issues with insertion of toolsinto the proximal opening. Generally speaking, wide proximal tails 238can be longer than proximal tails 238 that taper down to the width ofthe proximal control element 230.

A proximal region of the distal luminal portion 222 can incorporate oneor more markers to provide visualization under fluoro duringloading/reloading of the catheter advancement element 300. For example,the proximal end region can include a region of Pebax (e.g. 35D) loadedwith tungsten (80%) for radiopacity. In some implementations, theproximal tail 228 and/or the transition section 226 defining theproximal opening into the lumen of the luminal portion 222 can be coatedor embedded with a radiopaque material such that the opening into thelumen can be fully visualized during use. The radiopaque materialembedded in this proximal end region can create a step-up in outerdiameter.

The distal end of the proximal control element 230 and/or the distalluminal portion 222 may have features that facilitate a mechanical jointduring a weld, such as a textured surface, protruding features, orcut-out features. During a heat weld process, the features wouldfacilitate a mechanical bond between the polymer distal luminal portion222 and the proximal control element 230. For example, as shown in FIGS.6A-6F the proximal end of the distal luminal portion 222 can include ashort mating sleeve 240 coupled to a proximal edge 221 of the distalluminal portion 222. The sleeve 240 can include an inner lumen extendingbetween a proximal opening 242 and a distal opening 241. The distal endof the proximal control element 230 can insert through the proximalopening 242 and within the inner lumen of the sleeve 240 to couple theproximal control element 230 to the distal luminal portion 222. In someimplementations, the proximal control element 230 can couple with thedistal luminal portion 222 such that a distal opening 231 of thehypotube forming the proximal control element 230 can communicate withthe lumen 223 of the distal luminal portion 222, for example, throughthe distal opening 241 of the sleeve 240. The sleeve 240 can alsoprovide transition between distal luminal portion 222 and proximalcontrol element 230 similar to the proximal tail 238. The distal luminalportion 222 need not include a mating sleeve 240 to couple with theproximal control element 230. For example, the distal end of theproximal control element 230 can insert through a wall of the proximaltail 238 at the proximal end of the distal luminal portion 222 (see FIG.5A, 5E-5F). The distal end of the proximal control element 230 canextend along the length of the proximal tail 238 and along at least alength of the wall of the distal luminal portion 222.

The luminal portion 222 of the catheter 200 can have a uniform diameteror wall thickness from a proximal end to a distal end or the luminalportion 222 can have different outer diameters or wall thicknesses alongits length. For example, the distal-most end of the distal luminalportion 222 can have a smaller outer diameter compared to a moreproximal region of the distal luminal portion 222. FIGS. 5A-5B, 5E-5F aswell as FIGS. 6A-6B, 6E-6F, and FIG. 8A show a distal luminal portion222 having a distal tubular region or distal tube 245 having a smallerouter diameter and a proximal tubular region or proximal tube 246 have alarger outer diameter. The distal tube 245 transitions via a step-up 247to the proximal tube 246. As best shown in FIGS. 5A and 6A, the innerdiameters of distal tube 245 and the proximal tube 246 are substantiallythe same providing a smooth inner wall surface for the lumen 223. Theouter diameter of the distal tube 245 may be smaller than the outerdiameter of the proximal tube 246. The step-up 247 is formed by atransition in wall thickness between the distal tube 245 and theproximal tube 246. In some implementations, the outer diameter of thedistal tube 245 can be about 0.080″ to about 0.084″ and the outerdiameter of the proximal tube 246 can be about 0.087″ to about 0.088″.In other implementations, the outer diameter of the proximal tube 246can be 0.106″ to about 0.107″. The relative lengths of the proximal anddistal tubes 245, 246 may vary as described elsewhere herein. Forexample, the proximal tube 246 can create a proximal sealing zone thatis a cylindrical segment having a length that is about 1 mm, 2 mm, 3 mm,4 mm, 5 mm, up to about 10 mm, or 15 mm. The proximal sealing zone ofthe proximal tube 246 may have a larger OD compared to the OD of thedistal tube. In some implementations, the distal tube may have an ODthat is about 0.082″, the proximal tube 246 at the proximal sealing zonemay have an OD that is about 0.087″. In other implementations, where thedistal tube may have an OD that is about 0.102″, and the proximal tube246 at the proximal sealing zone may have an OD that is about 0.105″.

At least a portion of the wall of the larger outer diameter proximaltube 246 can be discontinuous such that it includes a slit 236 (seeFIGS. 5A-5C, 5E-5F, 6A-6C, and 6E-6F). The slit 236 can extend adistance along the length of the proximal tube 246. The slit 236 canextend from an edge 221 of the proximal tube 246 at least about 2 cm ofa length of the proximal tube 246. The slit 236 can, but need not,extend along the entire length of the proximal tube 246 to the locationof the step-up 247. Additionally, the proximal tube 246 can include morethan one slit 236. The slit 236 can be positioned in the larger diameterproximal tube 246 at a location opposite from where the distal end ofthe proximal control element 230 couples with the wall of the distalluminal portion 222. As such that distal end of the proximal controlelement 230 embedded within the wall of the proximal tube 246 liesopposite the slit 236 (see FIGS. 5C and 6C). The slit 236 can bepositioned around the proximal tube 246 at another location.

The slit 236 can allow for the proximal tube 246 to expand slightly suchthat the ends of the wall forming the slit 236 separate forming a gaptherebetween. For example, upon insertion of the catheter 200 throughthe working lumen of the sheath 400, the outer diameter can be receivedin a sliding fit such that at least an overlap region 348 remains. Uponapplication of an aspirational force through the working lumen, forexample, by applying suction from an aspiration source coupled to theproximal end 403 of the guide sheath 400, the sealing provided at theoverlap region 348 can be enhanced by a slight widening of the gapformed by the slit 236. This slight expansion provides for bettersealing between the outer diameter of the proximal tube 246 and theinner diameter of the working lumen of the sheath 400 because the outersurface of the walls of the catheter 200 can press against the innersurface of the working lumen creating a tight fit between the catheter200 and the sheath 400. This improved sealing between the outer surfaceof the catheter 200 and the inner surface of the working lumen minimizesthe seepage of blood from the vessel into the working lumen directlythrough the distal opening 408. Thus, the larger outer diameter of theproximal tube 246 in combination with the slit 236 can enhance sealingbetween the catheter 200 and the sheath 400 by accommodating forvariations of sheath inner diameters. The slit 236 can effectivelyincrease the outer diameter of the proximal tube 246 depending onwhether the walls forming the slit 236 are separated a distance. Thewalls forming the slit 236 can separate away from one another andincrease a width of slit. The outer diameter of the proximal tube 246including the increased width upon separation of the walls forming theslit 236 can be the same size or larger than the inner diameter of thesheath through which the proximal tube 246 is inserted. This allows fora single catheter to be compatible with a larger range of innerdiameters. In some implementations, the outer diameter of the proximaltube 246 can be 0.081″ or about 0.100″ when the walls forming the slit236 abut one another and no gap is present. The outer diameter of theproximal tube 246 can increase up to about 0.087″ or up to about 0.106″when the walls forming the slit 236 are separated a maximum distanceaway from one another. Additionally, the increased wall thickness of theproximal tube 246 allows for creating a more robust joint between thedistal luminal portion 222 and the proximal control element 230 of thecatheter.

Additionally or alternatively, the distal tip 406 of the sheath 400 caninclude one or more features that improve sealing between the innerdiameter of the working lumen of the sheath 400 and the outer diameterof the proximal end region of the catheter 200.

Catheter Advancement Element

The distal access system 100 can, but need not, include a catheteradvancement element 300 for delivery of the catheter 200 to the distalanatomy. Similarly, the catheter advancement element 300 can be usedtogether to advance other catheters besides the catheter 200 describedherein. For example, the catheter advancement element 300 can be used todeliver a 5 MAX Reperfusion Catheter (Penumbra, Inc. Alameda, Calif.)for clot removal in patients with acute ischemic stroke or otherreperfusion catheters known in the art. Although the catheteradvancement element 300 is described herein in reference to catheter 200it can be used to advance other catheters and it is not intended to belimiting to its use.

The distal access system 100 is capable of providing quick and simpleaccess to distal target anatomy, particularly the tortuous anatomy ofthe cerebral vasculature. The flexibility and deliverability of thedistal access catheter 200 allow the catheter 200 to take the shape ofthe tortuous anatomy and avoids exerting straightening forces creatingnew anatomy. The distal access catheter 200 is capable of this even inthe presence of the catheter advancement element 300 extending throughits lumen. Thus, the flexibility and deliverability of the catheteradvancement element 300 is on par or better than the flexibility anddeliverability of the distal luminal portion 222 of the distal accesscatheter 200 in that both are configured to reach the middle cerebralartery (MCA) circulation without straightening out the curves of theanatomy along the way.

The catheter advancement element 300 can include a non-expandable,flexible elongate body 360 coupled to a proximal portion 366. Thecatheter advancement element 300 and the catheter 200 described hereinmay be configured for rapid exchange or over-the-wire methods. Forexample, the flexible elongate body 360 can be a tubular portionextending the entire length of the catheter advancement element 300 andcan have a proximal opening from the lumen of the flexible elongate body360 that is configured to extend outside the patient's body during use.Alternatively, the tubular portion can have a proximal openingpositioned such that the proximal opening remains inside the patient'sbody during use. The proximal portion 366 can be a proximal elementcoupled to a distal tubular portion and extending proximally therefrom.A proximal opening from the tubular portion can be positioned near wherethe proximal element couples to the tubular portion. Alternatively, theproximal portion 366 can be a proximal extension of the tubular portionhaving a length that extends to a proximal opening near a proximalterminus of the catheter advancement element 300 (i.e. outside apatient's body).

The configuration of the proximal portion 366 can vary. In someimplementations, the proximal portion 366 is simply a proximal extensionof the flexible elongate body 360 that does not change significantly instructure but in flexibility. For example, the proximal portion 366transitions from the very flexible distal regions of the catheteradvancement element 300 towards less flexible proximal regions of thecatheter advancement element 300. The proximal portion 366 provides arelatively stiff proximal end suitable for manipulating and torqueingthe more distal regions of the catheter advancement element 300. Inother implementations, the proximal portion 366 is a hypotube. Thehypotube may be exposed or may be coated by a polymer. In still furtherimplementations, the proximal portion 366 may be a polymer portionreinforced by a coiled ribbon. The proximal portion 366 can have thesame outer diameter as the flexible elongate body or can have a smallerouter diameter as the flexible elongate body.

The proximal portion 366 need not include a lumen. For example, theproximal portion 366 can be a solid rod, ribbon, or wire have no lumenextending through it that couples to the tubular elongate body 360.Where the proximal portion 366 is described herein as having a lumen, itshould be appreciated that the proximal portion 366 can also be solidand have no lumen. The proximal portion 366 is generally less flexiblethan the elongate body 360 and can transition to be even more stifftowards the proximal-most end of the proximal portion 366. Thus, thecatheter advancement element 300 can have an extremely soft and flexibledistal-most tip that transitions proximally to a stiff proximal portion366 well suited for torqueing and pushing the distal elongate body 360.The transition in flexibility of the catheter advancement element 300and the system as a whole is described in more detail below and in theExamples.

The elongate body 360 can be received within and extended through theinternal lumen 223 of the distal luminal portion 222 of the catheter 200(see FIG. 2B). The elongate body 360 or tubular portion can have anouter diameter. The outer diameter of the tubular portion can have atleast one snug point, a difference between the inner diameter of thecatheter 200 and the outer diameter of the tubular portion at the snugpoint can be no more than about 0.010″, for example, from 0.003″ up toabout 0.010″, preferably about 0.006″ to about 0.008″. As will bedescribed in more detail below, the catheter advancement element 300 canalso include a tip portion or distal tip 346 located distal to the atleast one snug point of the tubular portion. The tip portion can have alength and taper along at least a portion of the length. The distal tip346 of the catheter advancement element 300 can be extended beyond thedistal end of the catheter 200 as shown in FIG. 2B. The proximal portion366 of the catheter advancement element 300 or proximal extension iscoupled to a proximal end region of the elongate body 360 and extendsproximally therefrom. The proximal portion 366 can be less flexible thanthe elongate body 360 and configured for bi-directional movement of theelongate body 360 of the catheter advancement element 300 within theluminal portion 222 of the catheter 200, as well as for movement of thecatheter system 100 as a whole. The elongate body 360 can be inserted ina coaxial fashion through the internal lumen 223 of the luminal portion222. The outer diameter of at least a region of the elongate body 360can be sized to substantially fill at least a portion of the internallumen 223 of the luminal portion 222.

The overall length of the catheter advancement element 300 (e.g. betweenthe proximal end through to the distal-most tip) can vary, but generallyis long enough to extend through the support catheter 200 plus at leasta distance beyond the distal end of the support catheter 200 while atleast a length of the proximal portion 366 remains outside the proximalend of the guide sheath 400 and outside the body of the patient. In someimplementations, the overall length of the catheter advancement element300 is about 145 to about 150 cm and has a working length of about 140cm to about 145 cm from a proximal tab or hub to the distal-most tip.The elongate body 360 can have a length that is at least as long as theluminal portion 222 of the catheter 200 although the elongate body 360can be shorter than the luminal portion 222 so long as at least aminimum length remains inside the luminal portion 222 when a distalportion of the elongate body 360 is extended distal to the distal end ofthe luminal portion 222 to form a snug point or snug region with thecatheter. In some implementations, this minimum length of the elongatebody 360 that remains inside the luminal portion 222 when the distal tip346 is positioned at its optimal advancement configuration is at leastabout 5 cm, at least about 6 cm, at least about 7 cm, at least about 8cm, at least about 9 cm, at least about 10 cm, at least about 11 cm, orat least about 12 cm up to about 50 cm. In some implementations, theshaft length of the distal luminal portion 222 can be about 35 cm up toabout 75 cm and shorter than a working length of the guide sheath andthe insert length of the elongate body 360 can be at least about 45 cm,46 cm, 47 cm, 48 cm, 48.5 cm, 49 cm, 49.5 cm up to about 85 cm.

The length of the elongate body 360 can allow for the distal end of theelongate body 360 to reach cerebrovascular targets within, for example,the M1 or M2 regions while the proximal end region of the elongate body360 remains proximal to or below the level of severe turns along thepath of insertion. For example, the entry location of the cathetersystem can be in the femoral artery and the target embolus can be distalto the right common carotid RCC artery, such as within the M1 segment ofthe middle cerebral artery on the right side. The proximal end region ofthe elongate body 360 where it transitions to the proximal portion 366can remain within a vessel that is proximal to severely tortuous anatomysuch as the carotid siphon, the right common carotid RCC artery, thebrachiocephalic trunk BT, the take-off into the brachiocephalic arteryfrom the aortic arch, the aortic arch AA as it transitions from thedescending aorta DA. This avoids inserting the stiffer proximal portion366, or the material transition between the stiffer proximal portion 366and the elongate body 360, from taking the turn of the aortic arch orthe turn of the brachiocephalic take-off from the aortic arch, whichboth can be very severe. The lengths described herein for the distalluminal portion 222 also can apply to the elongate body 360 of thecatheter advancement element.

The proximal portion 366 can have a length that varies as well. In someimplementations, the proximal portion 366 is about 90 cm up to about 95cm. The distal portion extending distal to the distal end of the luminalportion 222 can include distal tip 346 that protrudes a length beyondthe distal end of the luminal portion 222 during use of the catheteradvancement element 300. The distal tip 346 of the elongate body 360that is configured to protrude distally from the distal end of theluminal portion 222 during advancement of the catheter 200 through thetortuous anatomy of the cerebral vessels, as will be described in moredetail below. The proximal portion 366 coupled to and extendingproximally from the elongate body 360 can align generally side-by-sidewith the proximal control element 230 of the catheter 200. Thearrangement between the elongate body 360 and the luminal portion 222can be maintained during advancement of the catheter 200 through thetortuous anatomy to reach the target location for treatment in thedistal vessels and aids in preventing the distal end of the catheter 200from catching on tortuous branching vessels, as will be described inmore detail below.

In some implementations, the elongate body 360 can have a region ofrelatively uniform outer diameter extending along at least a portion ofits length and the distal tip 346 tapers down from the uniform outerdiameter. The outer diameter of the elongate body 360 can include astep-down at a location along its length, for example, a step-down inouter diameter at a proximal end region where the elongate body 360couples to the proximal portion 366. Depending upon the inner diameterof the catheter 200, the clearance between the catheter 200 and theouter diameter of the elongate body 360 along at least a portion of itslength can be no more than about 0.010″, such as within a range of about0.003″-0.010″ or between 0.006″-0.008″.

The elongate body 360 can have an overall shape profile from proximalend to distal end that transitions from a first outer diameter having afirst length to a tapering outer diameter having a second length. Thefirst length of this first outer diameter region (i.e. the snug-fittingregion between the distal luminal portion 222 and the elongate body 360)can be at least about 5 cm, or 10 cm, up to about 50 cm. The length ofthe tapering outer diameter can be between 1 cm and 4 cm. When thecatheter advancement element 300 is inserted through the catheter 200,this tapered distal tip 346 is configured to extend beyond and protrudeout through the distal end of the luminal portion 222 whereas the moreproximal region of the body 360 (i.e. the first length described above)remains within the luminal portion 222.

As mentioned, the distal end of the luminal portion 222 can be blunt andhave no change in the dimension of the outer diameter whereas the distaltip 346 can be tapered providing an overall elongated tapered geometryof the catheter system. The outer diameter of the elongate body 360 alsoapproaches the inner diameter of the luminal portion 222 such that thestep-up from the elongate body 360 to the outer diameter of the luminalportion 222 is minimized. Minimizing this step-up prevents issues withthe lip formed by the distal end of the luminal portion 222 catching onthe tortuous neurovasculature, such as around the carotid siphon nearthe ophthalmic artery branch, when the distal tip 346 in combinationwith the distal end region of the catheter 200 bends and curves alongwithin the vascular anatomy. In some implementations, the inner diameterof the luminal portion 222 can be at least about 0.052″, about 0.054″and the maximum outer diameter of the elongate body 360 can be about0.048″ such that the difference between them is about 0.006″. In someimplementations, the inner diameter of the luminal portion 222 can beabout 0.070″ and the maximum outer diameter of the elongate body 360 canbe about 0.062″ such that the difference between them is about 0.008″.In some implementations, the inner diameter of the luminal portion 222can be about 0.088″ and the maximum outer diameter of the elongate body360 can be about 0.080″ such that the difference between them is about0.008″. In some implementations, the inner diameter of the luminalportion 222 can be about 0.072″ and the maximum outer diameter of theelongate body 360 is about 0.070″ such that the difference between themis only 2 thousandths of an inch. In other implementations, the maximumouter diameter of the elongate body 360 is about 0.062″ such that thedifference between them is about 0.010″. Despite the outer diameter ofthe elongate body 360 extending through the lumen of the luminal portion222, the luminal portion 222 and the elongate body 360 extending throughit in co-axial fashion are flexible enough to navigate the tortuousanatomy leading to the level of M1 or M2 arteries without kinking andwithout damaging the vessel.

The dimensions provided herein are approximate and each dimensions mayhave an engineering tolerance or a permissible limit of variation. Useof the term “about” or “approximately” are intended to provide suchpermissible tolerance to the dimension being referred to. Where “about”or “approximately” is not used with a particular dimension herein thatthat dimension need not be exact.

The length of the distal tip 346 (e.g. the region of the catheteradvancement element 300 configured to extend distal to the distal end ofthe catheter 200 during use to obtain the optimum advancementconfiguration) can vary. In some implementations, the length of thedistal tip 346 can be in a range of between about 0.50 cm to about 4.0cm from the distal-most terminus of the elongate body 360 or betweenabout 1.0 cm to about 3.0 cm. In other implementations, the length ofthe distal tip 346 is between 2.0 cm to about 2.5 cm. In someimplementations, the length of the distal tip 346 varies depending onthe inner diameter of the catheter 200 with which the catheteradvancement element 300 is to be used. For example, the length of thedistal tip 346 can be as shorter (e.g. 1.2 cm) for a catheteradvancement element 300 sized to be used with a catheter 200 having aninner diameter of about 0.054″ and can be longer (e.g. 2.5 cm) for acatheter advancement element 300 sized to be used with a catheter 200having an inner diameter of about 0.088″. The distal tip 346 can be aconstant taper from the outer diameter of the elongate body 360 (e.g.the distal end of the marker 344 b) down to a second smaller outerdiameter at the distal-most terminus (e.g. the proximal end of themarker 344 a) as shown in FIG. 7C. In some implementations, the constanttaper of the distal tip 346 can be from about 0.048″ outer diameter downto about 0.031″ outer diameter over a length of about 1 cm. In someimplementations, the constant taper of the distal tip 346 can be from0.062″ outer diameter to about 0.031″ outer diameter over a length ofabout 2 cm. In still further implementations, the constant taper of thedistal tip 346 can be from 0.080″ outer diameter to about 0.031″ outerdiameter over a length of about 2.5 cm. The length of the constant taperof the distal tip 346 can vary, for example, between 0.8 cm to about 2.5cm, or between 1 cm and 3 cm, or between 2.0 cm and 2.5 cm. The angle ofthe taper can vary depending on the outer diameter of the elongate body360. For example, the taper can be between 0.9 to 1.6 degree anglerelative to horizontal. The taper can be between 2-3 degree angle from acenter line of the elongate body 360.

The catheter advancement element 300 can include a distal tip 346 thattapers over a length. The elongate body 360 of the catheter advancementelement 300 can have an inner diameter that does not change over itslength even in the presence of the tapering of the distal tip 346. Thus,the inner diameter of the lumen extending through the tubular portion ofthe catheter advancement element 300 can remain uniform and the wallthickness of the distal tip 346 can decrease to provide the taper. Thewall thickness can thin distally along the length of the taper. Thus,the material properties in combination with wall thickness, angle,length of the taper can all contribute to the overall maximumflexibility of the distal-most end of the distal tip 346. The catheteradvancement element 300 undergoes a transition in flexibility from thedistal-most end towards the snug point where it achieves an outerdiameter that is no more than about 0.010″ different from the innerdiameter of the catheter 200.

The distal tip 346 need not taper and can achieve its soft, atraumaticand flexible characteristic due to a material property other than due toa change in outer dimension to facilitate endovascular navigation to anembolus in tortuous anatomy. Additionally or alternatively, the distaltip 346 of the elongate body 360 can have a transition in flexibilityalong its length. The most flexible region of the distal tip 346 can beits distal terminus. Moving along the length of the distal tip 346 fromthe distal terminus towards a region proximal to the distal terminus.For example, the distal tip 346 can be formed of a material having amaterial hardness of no more than 35D or about 62A and transitionsproximally to be less flexible near where it is formed of a materialhaving a material hardness of no more than 55D and 72D up to theproximal portion 366, which can be a stainless steel hypotube, or acombination of a material property and tapered shape. The materials usedto form the regions of the elongate body 360 can include PEBAX (such asPEBAX 25D, 35D, 55D, 72D) with a lubricious additive compound, such asMobilize (Compounding Solutions, Lewiston, Me.). In someimplementations, the material used to form a region of the elongate body360 can be Tecothane 62A. Incorporation of a lubricious additivedirectly into the polymer elongate body means incorporation of aseparate lubricious liner, such as a Teflon liner, is unnecessary. Thisallows for a more flexible element that can navigate the distal cerebralanatomy and is less likely to kink. Similar materials can be used forforming the distal luminal portion 222 of the catheter 200 providingsimilar advantages. The flexibility of the distal tip 346 can beachieved by a combination of flexible lubricious materials and taperedshapes. For example, the length of the tip 346 can be kept shorter than2 cm-3 cm, but maintain optimum deliverability due to a change inflexible material from distal-most tip towards a more proximal region adistance away from the distal-most tip. In an implementation, theelongate body 360 is formed of PEBAX (polyether block amide) embeddedsilicone designed to maintain the highest degree of flexibility. Thewall thickness of the distal end of the luminal portion 222 can also bemade thin enough such that the lip formed by the distal end of theluminal portion 222 relative to the elongate body 360 is minimized.

The elongate body 360 has a benefit over a microcatheter in that it canhave a relatively large outer diameter that is just 0.003″-0.010″smaller than the inner diameter of the distal luminal portion 222 of thecatheter 200 and still maintaining a high degree of flexibility fornavigating tortuous anatomy. When the gap between the two components istoo tight (e.g. less than about 0.003″), the force needed to slide thecatheter advancement element 300 relative to the catheter 200 can resultin damage to one or both of the components and increases risk to thepatient during the procedure. The gap results in too tight of a fit toprovide optimum relative sliding. When the gap between the twocomponents is too loose (e.g. greater than about 0.010″), the distal endof the catheter 200 forms a lip that is prone to catch on branchingvessels during advancement through tortuous neurovasculature, such asaround the carotid siphon where the ophthalmic artery branches off.

The gap in ID/OD between the elongate body 360 and the distal luminalportion 222 can be in this size range (e.g. 0.003″-0.010″) along amajority of their lengths. For example, the elongate body 360 can have arelatively uniform outer diameter that is between about 0.048″ to about0.080″ from a proximal end region to a distal end region up to a pointwhere the taper of the distal tip 346 begins. Similarly, the distalluminal portion 222 of the catheter 200 can have a relatively uniforminner diameter that is between about 0.054″ to about 0.088″ from aproximal end region to a distal end region. As such, the differencebetween their respective inner and outer diameters along a majority oftheir lengths can be within this gap size range of 0.003″ to 0.010″. Thedistal tip 346 of the elongate body 360 that is tapered will have alarger gap size relative to the inner diameter of the distal luminalportion 222. During use, however, this tapered distal tip 346 isconfigured to extend distal to the distal end of the catheter 200 suchthat the region of the elongate body 360 having an outer diameter sizedto match the inner diameter of the distal luminal portion 222 ispositioned within the lumen of the catheter 200 such that it canminimize the lip at the distal end of the catheter 200.

The elongate body 360 can be formed of various materials that provide asuitable flexibility and lubricity. Example materials include highdensity polyethylene, 72D PEBAX, 90D PEBAX, or equivalent stiffness andlubricity material. At least a portion of the elongate body 360 can bereinforced to improve navigation and torqueing (e.g. braidedreinforcement layer). The flexibility of the elongate body 360 canincrease towards the distal tip 346 such that the distal region of theelongate body 360 is softer, more flexible, and articulates and bendsmore easily than a more proximal region. For example, a more proximalregion of the elongate body can have a bending stiffness that isflexible enough to navigate tortuous anatomy such as the carotid siphonwithout kinking. If the elongate body 360 has a braid reinforcementlayer along at least a portion of its length, the braid reinforcementlayer can terminate a distance proximal to the distal tip 346. Forexample, the distance from the end of the braid to the distal tip can beabout 10 cm to about 15 cm or from about 4 cm to about 10 cm or fromabout 4 cm up to about 15 cm.

In some implementations, the elongate body 360 can be generally tubularalong at least a portion of its length such that it has a single lumen368 extending parallel to a longitudinal axis of the catheteradvancement element 300 (see FIG. 7A-7C and also FIG. 10A-10C). In animplementation, the single lumen 368 of the elongate body 360 is sizedto accommodate a guidewire, however use of the catheter advancementelement 300 generally eliminates the need for a guidewire lead. Methodsof using the catheter advancement element 300 without a guidewire todeliver a catheter to distal regions of the brain are described in moredetail below.

A guidewire can extend through the single lumen 368 generallyconcentrically from a proximal opening to a distal opening through whichthe guidewire can extend. In some implementations, the proximal openingis at the proximal end of the catheter advancement element 300 such thatthe catheter advancement element 300 is configured for over-the-wire(OTW) methodologies. In other implementations, the proximal opening is arapid exchange opening 362 through a wall of the catheter advancementelement 300 such that the catheter advancement element 300 is configuredfor rapid exchange rather than or in addition to OTW. In thisimplementation, the proximal opening 362 extends through the sidewall ofthe elongate body and is located a distance away from a proximal tab 364and distal to the proximal portion 366 (see FIGS. 7A-7B and 7D). Theproximal opening 362 can be located a distance of about 10 cm from thedistal tip 346 up to about 20 cm from the distal tip 346. In someimplementations, the proximal opening 362 can be located near a regionwhere the elongate body 360 is joined to the proximal portion 366, forexample, just distal to an end of the hypotube (see FIG. 7B). In otherimplementations, the proximal opening 362 is located more distally suchas about 10 cm to about 18 cm from the distal-most end of the elongatebody 360 (see FIG. 7D). A proximal opening 362 that is located closer tothe distal tip 346 allows for easier removal of the catheter advancementelement 300 from the catheter 200 leaving the guidewire in place for a“rapid exchange” type of procedure. Rapid exchanges can rely on only asingle person to perform the exchange. The catheter advancement element300 can be readily substituted for another device using the sameguidewire that remains in position. The single lumen 368 of the elongatebody 360 can be configured to receive a guidewire in the range of 0.014″and 0.018″ diameter, or in the range of between 0.014″ and 0.022″. Inthis implementation, the inner luminal diameter of the elongate body 360can be between 0.020″ and 0.024″. The guidewire, the catheteradvancement element 300, and the catheter 200 can all be assembledco-axially for insertion through the working lumen of the guide sheath400. The inner diameter of the lumen 368 of the elongate body 360 can be0.019″ to about 0.021″.

FIG. 7D shows another implementation of the catheter advancement element300 configured for rapid exchange. Rapid exchange configurations candramatically shorten device length, decreases staffing requirements, andreduces fluoroscopy. As with other implementations described herein, thecatheter advancement element 300 can include a non-expandable, flexibleelongate body 360 coupled to a proximal portion 366 coupled to aproximal tab 364 or hub 375. The region near the distal tip 346 can betapered such that the outer diameter tapers over a length of about 1 cmto about 4 cm. In some implementations, the distal taper length is 2.5cm. In some implementations, the distal tip 346 tapers from about 0.080″to about 0.031″. Also, the distal tip 346 can be formed of a materialhaving a material hardness (e.g. 62A and 35D) that transitionsproximally towards increasingly harder materials having (e.g. 55D and72D) up to the proximal portion 366. For example, FIG. 7D illustratessegment 371 of the elongate body 360 including the distal tip 346 formedof a material having a material hardness of 35D and a length of about 10cm to about 12.5 cm. Segment 371 of the elongate body 360 including thedistal tip 346 formed of a material having a material hardness of 62Aand a length of about 10 cm to about 12.5 cm. Segment 372 of theelongate body 360 formed of a material having a material hardness of 55Dand have a length of about 5 cm to about 8 cm. Segment 373 of theelongate body 360 formed of a material having a material hardness of 72Dcan be about 25 cm to about 35 cm in length. The three segments 371,372, 373 combined can form an insert length of the elongate body 360from where the proximal portion 366 couples to the elongate body 360 tothe terminus of the distal tip 346 that can be about 49 cm in length.

FIGS. 10A-10C illustrate an implementation of a catheter advancementelement 300 incorporating a reinforcement layer 380. The reinforcementlayer 380 can be a braid or other type of reinforcement to improve thetorqueability of the catheter advancement element 300 and help to bridgethe components of the catheter advancement element 300 having suchdifferences in flexibility. The reinforcement layer 380 can bridge thetransition from the rigid, proximal portion 366 to the flexible elongatebody 360. In some implementations, the reinforcement layer 380 can be abraid positioned between inner and outer layers of Pebax 382, 384 (seeFIG. 10C). The reinforcement layer 380 can terminate a distance proximalto the distal tip portion 346. For example, FIG. 10A illustrates theelongate body 360 having segment 371 and segment 373 located proximal tosegment 371. Segment 371 can include the distal tip 346 formed of amaterial having a material hardness of at most about 35D. Segment 371 isunreinforced polymer having a length of about 4 cm up to about 12.5 cm.Segment 373 of the elongate body 360 located proximal to segment 371 caninclude the reinforcement layer 380 and can extend a total of about 37cm up to the unreinforced distal segment 371. A proximal end region ofthe reinforcement layer 380 can overlap with a distal end region of theproximal portion 366 such that a small overlap of hypotube andreinforcement exists near the transition between the proximal portion366 and the elongate body 360.

Again with respect to FIG. 7D, an entry port 362 for a proceduralguidewire can be positioned a distance away from the distal-most end ofthe elongate body 360. In some implementations, the entry/exit port 362can be about 18 cm from the distal-most end creating a rapid exchangewire entry/exit segment 370. The outer diameter of the elongate body 360within segment 370 (segments 371 and 372) can be about 0.080″-0.082″whereas segment 373 proximal to this rapid exchange wire entry/exitsegment 370 can have a step-down in outer diameter such as about0.062″-0.064″.

The tubular portion of the catheter advancement element can have anouter diameter that has at least one snug point. A difference betweenthe outer diameter at the snug point and the inner diameter of the lumenat the distal end of the distal, catheter portion can be no more thanabout 0.010″. The at least one snug point of this tubular portion can bea point along the length of the tubular portion. The at least one snugpoint of this tubular portion can have a length that is at least about 5cm up to about 50 cm, including for example, at least about 6 cm, atleast about 7 cm, at least about 8 cm, at least about 9 cm, at leastabout 10 cm, at least about 11 cm, or at least about 12 cm up to about50 cm. This length need not be uniform such that the length need not besnug alone its entire length. For example, the snug point region caninclude ridges, grooves, slits, or other surface features.

In other implementations, the entire catheter advancement element 300can be a tubular element configured to receive a guidewire through boththe proximal portion 366 as well as the elongate body 360. For example,the proximal portion 366 can be a hypotube or tubular element having alumen that communicates with the lumen 368 extending through theelongate body 360 (shown in FIG. 3). In some implementations, theproximal portion 366 can be a skived hypotube of stainless steel coatedwith PTFE having an outer diameter of 0.026″. In other implementations,the outer diameter can be between 0.024″ and 0.030″. In someimplementations, such as an over-the-wire version, the proximal portion366 can be a skived hypotube coupled to a proximal hub 375. The proximalportion 366 can extend eccentric or concentric to the distal luminalportion 222. As best shown in FIG. 7E, the proximal portion 366 can be astainless steel hypotube. The proximal portion 366 can be a solid metalwire that is round or oval cross-sectional shape. The proximal portion366 can be a flattened ribbon of wire having a rectangularcross-sectional shape. The ribbon of wire can be curved into a circular,oval, c-shape, or quarter circle, or other cross-sectional shape alongan arc. The proximal portion 366 can have any of variety ofcross-sectional shapes whether or not a lumen extends therethrough,including a circular, oval, C-shaped, D-shape, or other shape. In someimplementations, the proximal portion 366 is a hypotube having a D-shapesuch that an inner-facing side is flat and an outer-facing side isrounded. The rounded side of the proximal portion 366 can be shaped toengage with a correspondingly rounded inner surface of the sheath 400.The hypotube can have a lubricious coating such as PTFE. The hypotubecan have an inner diameter of about 0.021″, an outer diameter of about0.0275″, and an overall length of about 94 cm providing a working lengthfor the catheter advancement element 300 that is about 143 cm. Includingthe proximal hub 375, the catheter advancement element 300 can have anoverall length of about 149 cm. In some implementations, the hypotubecan be a tapered part with a length of about 100 mm, starting proximalwith a thickness of 0.3 mm and ending with a thickness of 0.10 mm to0.15 mm. In still further implementations, the elongate body 360 can bea solid element coupled to the proximal portion 366 having no guidewirelumen.

The proximal portion 366 is shown in FIGS. 2A, 7A-7D, and 10A as havinga smaller outer diameter compared to the outer diameter of the elongatebody 360. The proximal portion 366 need not step down in outer diameterand can also have the same outer diameter as the outer diameter as theelongate body 360. For example, the proximal portion 366 can incorporatea hypotube or other stiffening element that is coated by one or morelayers of polymer resulting in a proximal portion 366 havingsubstantially the same outer diameter as the elongate body 360.

As best shown in FIGS. 7F-7J, the proximal end of the proximal portion366 can be coupled to a proximal hub 375. The proximal hub 375 can be anover-molded component having a luer thread 377 and a luer taper 378formed on an inside of the proximal hub 375. The proximal hub 375 canincorporate a tab 364 providing for easier gripping by a user. Theproximal hub 375 prevents advancement of the catheter advancementelement 300 and the catheter 200 beyond the distal tip of the basesheath 400 or guide catheter by limiting insertion into the proximal RHV434 providing critical functional and safety features for properoperation of the system 10.

At least a portion of the solid elongate body 360, such as the elongatedistal tip 346, can be formed of or embedded with or attached to amalleable material that skives down to a smaller dimension at a distalend. The distal tip 346 can be shaped to a desired angle or shapesimilar to how a guidewire may be used. The malleable length of theelongate body 360 can be at least about 1 cm, 3 cm, 5 cm, and up toabout 10 cm, 15 cm, or longer. In some implementations, the malleablelength can be about 1%, 2%, 5%, 10%, 20%, 25%, 50% or more of the totallength of the elongate body 360. In some implementations, the catheteradvancement element 300 can have a working length of about 140 cm toabout 143 cm and the elongate body 360 can have an insert length ofabout 49 cm. The insert length can be the PEBAX portion of the elongatebody 360 that is about 49.5 cm. As such, the malleable length of theelongate body 360 can be between about 0.5 cm to about 25 cm or more.The shape change can be a function of a user manually shaping themalleable length prior to insertion or the tip can be pre-shaped at thetime of manufacturing into a particular angle or curve. Alternatively,the shape change can be a reversible and actuatable shape change suchthat the tip forms the shape upon activation by a user such that the tipcan be used in a straight format until a shape change is desired by theuser. The catheter advancement element 300 can also include a formingmandrel extending through the lumen of the elongate body 360 such that aphysician at the time of use can mold the distal tip 346 into a desiredshape. As such, the moldable distal tip 346 can be incorporated onto anelongate body 360 that has a guidewire lumen.

The elongate body 360 can extend along the entire length of the catheter200, including the distal luminal portion 222 and the proximal controlelement 230 or the elongate body 360 can incorporate the proximalportion 366 that aligns generally side-by-side with the proximal controlelement 230 of the catheter 200. The proximal portion 366 of theelongate body 360 can be positioned co-axial with or eccentric to theelongate body 360. The proximal portion 366 of the elongate body 360 canhave a lumen extending through it. Alternatively, the portion 366 can bea solid rod or ribbon having no lumen.

Again with respect to FIGS. 7A-7D, like the distal luminal portion 222of the catheter 200, the elongate body 360 can have one or moreradiopaque markers 344 along its length. The one or more markers 344 canvary in size, shape, and location. One or more markers 344 can beincorporated along one or more parts of the catheter advancement element300, such as a tip-to-tip marker, a tip-to-taper marker, an RHVproximity marker, a Fluoro-saver marker, or other markers providingvarious information regarding the relative position of the catheteradvancement element 300 and its components. In some implementations andas best shown in FIG. 7C, a distal end region can have a firstradiopaque marker 344 a and a second radiopaque marker 344 b can belocated to indicate the border between the tapering of the distal tip346 and the more proximal region of the elongate body 360 having auniform or maximum outer diameter. This provides a user with informationregarding an optimal extension of the distal tip 346 relative to thedistal end of the luminal portion 222 to minimize the lip at this distalend of the luminal portion 222 for advancement through tortuous anatomy.In other implementations, for example where the distal tip 346 is notnecessarily tapered, but instead has a change in overall flexibilityalong its length, the second radiopaque marker 344 b can be located toindicate the region where the relative flexibilities of the elongatebody 360 (or the distal tip 346 of the elongate body 360) and the distalend of the luminal portion 222 are substantially the same. The markermaterial may be a platinum/iridium band, a tungsten, platinum, ortantalum-impregnated polymer, or other radiopaque marker that does notimpact the flexibility of the distal tip 346 and elongate body 360. Insome implementations, the radiopaque markers are extruded PEBAX loadedwith tungsten for radiopacity. In some implementations, the proximalmarker band can be about 2.0 mm wide and the distal marker band can beabout 2.5 mm wide to provide discernable information about the distaltip 346.

The proximal control element 230 of the catheter 200 can include aproximal tab 234 on the proximal end of the proximal control element230. Similarly, the proximal portion 366 coupled to the elongate body360 can include a tab 364. The tabs 234, 364 can be configured toremovably and adjustable connect to one another and/or connect to theircorresponding proximal portions. The coupling allows the catheteradvancement element 300 to reversibly couple with the catheter 200 tolock (and unlock) the relative extension of the distal luminal portion222 and the elongate body 360. This allows the catheter 200 and thecatheter advancement element 300 to be advanced as a single unit. In thelocked configuration, the tab 364 or proximal portion 366 can be engagedwith the catheter tab 234. In the unlocked configuration, the tab 364may be disengaged from the catheter tab 234. The tab 364 or proximalportion 366 may attach, e.g., click or lock into, the catheter tab 234in a fashion as to maintain the relationships of corresponding sectionof the elongate body 360 and the catheter 200 in the lockedconfiguration. The tab 364 can be a feature on the proximal hub 375 suchas the hub 375 shown in FIGS. 7F-7J.

Such locking may be achieved by, e.g., using a detent on the tab 364that snaps into place within a recess formed in the catheter tab 234, orvice versa. For example, the tab 234 of the catheter 200 can form a ringhaving a central opening extending therethrough. The tab 364 of the body360 can have an annular detent with a central post sized to insertthrough the central opening of the tab 234 such that such that the ringof the tab 234 is received within the annular detent of tab 364 forminga singular grasping element for a user to advance and/or withdraw thecatheter system through the access sheath. The tabs 234, 364 may beaffixed or may be slideable to accommodate different relative positionsbetween the elongate body 360 and the luminal portion 222 of thecatheter 200. In some implementations, a proximal end of the proximalcontrol element 230 of the catheter 200 can include a coupling feature334, such as clip, clamp, c-shaped element or other connector configuredto receive the proximal portion 366 of the catheter advancement element300 (see FIG. 2A). The coupling feature 334 can be configured to snaptogether with the proximal portion 366 through an interference fit suchthat a first level of force is needed in order to insert the proximalportion 366 into the clip of the tab 234 and a second, greater level offorce is needed to remove the proximal portion 366 from the clip of thetab 234. However, upon inserting the proximal portion 366 into thecoupling feature 334 the catheter advancement element 300 and thecatheter 200 can still be slideably adjusted relative to one anotheralong a longitudinal axis of the system. The amount of force needed toslideably adjust the relative position of the two components can be suchthat inadvertent adjustment is avoided and the relative position can bemaintained during use, but can be adjusted upon conscious modification.The configuration of the coupling between the proximal portion 366 ofthe catheter advancement element 300 and the proximal control element230 of the catheter 200 can vary. Generally, however, the coupling isconfigured to be reversible and adjustable while still providingadequate holding power between the two elements in a manner that isrelatively user-friendly (e.g. allows for one-handed use) and organizesthe proximal ends of the components (e.g. prevents the proximal controlelement 230 and proximal portion 366 from becoming twisted and entangledwith one another). The coupling feature 334 configured to prevententanglement and aid in the organization of the proximal portions can beintegrated with the tabs or can be a separate feature located alongtheir proximal end region.

The catheter advancement element 300 can be placed in a lockedconfiguration with the catheter 200 configured for improved trackingthrough a tortuous and often diseased vasculature in acute ischemicstroke. Other configurations are considered herein. For example, theelongate body 360 can include one or more detents on an outer surface.The detents can be located near a proximal end region and/or a distalend region of the elongate body 360. The detents are configured to lockwith correspondingly-shaped surface features on the inner surface of theluminal portion 222 through which the elongate body 360 extends. Thecatheter advancement element 300 and the catheter 200 can haveincorporate more than a single point of locking connection between them.For example, a coupling feature 334, such as clip, clamp, c-shapedelement or other connector configured to hold together the catheteradvancement element 300 and proximal control element 230 or tab 234 ofthe catheter 200.

In some implementations, the proximal control element 230 of thecatheter 200 can run alongside or within a specialized channel of theproximal portion 366. The channel can be located along a length of theproximal portion 366 and have a cross-sectional shape that matches across-sectional shape of the catheter proximal control element 230 suchthat the proximal control element 230 of the catheter 200 can bereceived within the channel and slide smoothly along the channelbi-directionally. Once the catheter 200 and elongate body 360 are fixed,the combined system, i.e., the catheter 200-catheter advancement element300 may be delivered to a target site, for example through the workinglumen of the guide sheath 400 described elsewhere herein.

The catheter advancement element 300 (whether incorporating thereinforcement layer or not) loaded within the lumen of the catheter 200may be used to advance the catheter 200 to distal regions of the brain(e.g. level of the MCA). The traditional approach to the Circle ofWillis is to use a triaxial system including a guidewire placed within aconventional microcatheter placed within an intermediate catheter. Theentire coaxial system can extend through a base catheter or sheath. Thesheath is typically positioned such that the distal tip of the sheath isplaced in a high cervical carotid artery. The coaxial systems are oftenadvanced in unison up to about the terminal carotid artery where theconventional coaxial systems must then be advanced in a step-wisefashion in separate throws. This is due to the two sequential 180 degreeor greater turns (see FIGS. 1A-1C). The first 180 degree turn is at thelevel of the petrous to the cavernous internal carotid artery. Thesecond 180 degree turn is at the terminal cavernous carotid artery as itpasses through the bony elements and reaches the bifurcation into theanterior cerebral artery ACA and middle cerebral artery MCA. ThisS-shape region is referred to herein as the “siphon” or “carotidsiphon”. The ophthalmic artery arises from the cerebral ICA, whichrepresents a common point of catheter hang-up in accessing the anteriorcirculation.

Conventional microcatheter systems can be advanced through to theanterior circulation over a guidewire. The inner diameter of theconventional microcatheter is significantly larger than the outerdiameter of the guidewire over which it is advanced thereby forming alip on a distal end region of the system that can catch on these sidebranches during passage through the siphon. Conventional microcathetersystems (i.e. guidewire, microcatheter, and intermediate catheter) areadvanced through the bends of the carotid siphon sequentially to distaltarget sites rather than in a single, smooth pass. The bends of thecarotid siphon are taken one at a time in a step-wise advancementtechnique. For example, to pass through the carotid siphon, theconventional microcatheter is held fixed while the guidewire is advancedalone a first distance (i.e. through the first turn of the siphon).Then, the guidewire is held fixed while the conventional microcatheteris advanced alone through the first turn over the guidewire. Then, theconventional microcatheter and guidewire are held fixed while theintermediate catheter is advanced alone through the first turn over themicrocatheter and guidewire. The process repeats in order to passthrough the second turn of the siphon, which generally is considered themore challenging turn into the cerebral vessel. The microcatheter andintermediate catheter are held fixed while the guidewire is advancedalone a second distance (i.e. through the second turn of the siphon).Then, the guidewire and interventional catheter are held fixed while themicrocatheter is advanced alone through that second turn over theguidewire. Then, the guidewire and the microcatheter are held fixedwhile the interventional catheter is advanced alone through the secondturn. This multi-stage, step-wise procedure is a time-consuming processthat requires multiple people performing multiple hand changes on thecomponents. For example, two hands to fix and push the components overeach other forcing the user to stage the steps. The step-wise procedureis required because the stepped transitions between these components(e.g. the guidewire, microcatheter, and intermediate catheter) makesadvancement too challenging.

In contrast, the catheter 200 and catheter advancement element 300eliminate this multi-stage, step-wise component advancement procedure toaccess distal sites across the siphon. The catheter 200 and catheteradvancement element 300 can be advanced as a single unit through theboth turns of the carotid siphon CS. Both turns can be traversed in asingle smooth pass or throw to a target in a cerebral vessel without thestep-wise adjustment of their relative extensions and without relying onthe conventional step-wise advancement technique with conventionalmicrocatheters. The catheter 200 having the catheter advancement element300 extending through it allows a user to advance them in unison in thesame relative position from the first bend of the siphon through thesecond bend beyond the terminal cavernous carotid artery into the ACAand MCA. Importantly, the advancement of the two components can beperformed in a single smooth movement through both bends without anychange of hand position.

The catheter advancement element 300 can be in a juxtapositionedrelative to the catheter 200 that provides an optimum relative extensionbetween the two components for single smooth advancement. The catheteradvancement element 300 can be positioned through the lumen of thecatheter 200 such that its distal tip 346 extends beyond a distal end ofthe catheter 200. The distal tip 346 of the catheter advancement element300 eliminates the stepped transition between the inner member and theouter catheter 200 thereby avoiding issues with catching on branchingvessels within the region of the vasculature such that the catheter 200may easily traverse the multiple angulated turns of the carotid siphonCS. The optimum relative extension, for example, can be the distal tip346 of the elongate body 360 extending distal to a distal end of thecatheter 200. A length of the distal tip 346 extending distal to thedistal end of the catheter 200 during advancement can be between 0.5 cmand about 4 cm. This juxtaposition can be a locked engagement with amechanical element or simply by a user holding the two componentstogether.

The components can be advanced together with a guidewire, over aguidewire pre-positioned, or without any guidewire at all. In someimplementations, the guidewire can be pre-assembled with the catheteradvancement element 300 and catheter 200 such that the guidewire extendsthrough a lumen of the catheter advancement element 300, which is loadedthrough a lumen of the catheter 200, all prior to insertion into thepatient. The pre-assembled components can be simultaneously insertedinto the sheath 400 and advanced together up through and past the turnsof the carotid siphon.

The optimum relative extension of the catheter 200 and catheteradvancement element 300 can be based additionally on the staggering ofmaterial transitions. FIG. 11 is a schematic illustrating approximatelocations of the material transitions in the catheter advancementelement 300 and the approximate locations of the material transitions inthe catheter 200. For example, the catheter advancement element 300 caninclude a proximal portion 366, which can be a hypotube, having amaterial hardness of approximately 72D. The proximal portion 366transitions at a location 1101 a to a region having a material hardnessof about 55D that transitions at a location 1101 b to a region having amaterial hardness of about 35D that transitions at a location 1101 c toa region have a material hardness of 35D. Similarly, the catheter 200can include a proximal control element 230 that is a stainless steelribbon. The proximal control element 230 transitions at a location 1103a to a region having a material hardness of 72D that transitions at alocation 1103 b to a region having a hardness of 55D that transitions ata location 1103 c to a region having a material hardness of about 40Dthat transitions at a location 1103 d to a region having a materialhardness of about 35D that transitions at a location 1103 e to a regionhave a material hardness of 25D that transitions at a location 1103 f toa region having a material hardness of about 85A that transitions at alocation 1103 g to a region having a material hardness of about 80A. Adistal-most region of the catheter advancement element 300 can be formedof Tecothane having a material hardness of about 62A. The locations 1101of the catheter advancement element 300 and the locations 1103 of thecatheter 200 can be staggered such that the locations are off-set fromone another. More or fewer material transitions may exist within thecatheter advancement element and catheter.

The catheter 200 and catheter advancement element 300 can bepre-assembled at the time of manufacturing such that an optimum lengthof the catheter advancement element 300 extends distal to the distal endof catheter 200 and/or the material transitions are staggered. Anoptimum length of extension can be such that the entire length of thetapered distal tip of the catheter advancement element 300 extendsoutside the distal end of the catheter 200 such that the outer diameterof the catheter advancement element 300 where the at least one snugpoint is located aligns substantially with the distal end of thecatheter 200. This can result in the snug outer diameter region of theelongate body 360 aligned substantially with the distal end of thecatheter 200 such that it remains inside the lumen of the catheter 200and only the tapered region of the distal tip 346 extends distal to thelumen of the catheter 200. This relative arrangement provide the bestarrangement for advancement through tortuous vessels where a lip at thedistal end of the system would pose the greatest difficulty. Thisoptimal pre-assembled arrangement can be maintained by a couplerconfigured to engage with both the proximal control element 230 of thecatheter 200 and the proximal portion 366 of the catheter advancementelement 300. The coupler can be used during a procedure. Alternatively,the coupler can be removed prior to a procedure.

Different regions of the distal luminal portion 222 and the elongatebody 360 of the catheter advancement element 300 can have differentbending stiffness. Bending stiffness in N-mm² can be measured byassessing the force in Newtons (N) generated upon deflecting the devicea certain distance using a particular gauge length. FIG. 12 is aschematic of a testing system 1205 for assessing bending stiffness orbending force of the various components described herein. The testingsystem 1205 can vary as is known in the art. The testing system shown inFIG. 12 includes a pin 1210 forming a fixed point, an anvil 1215connected by a lever 1222 to a strain gauge 1220 forming a gauge point.The pin 1210 can hold the specimen 1201 to be tested such that a gaugelength 1225 of the specimen 1201 is exposed. The anvil 1215 is attachedto the strain gauge 1220 via the lever 1222 and can be urged against aportion of the specimen 1201 that is positioned away from the pin 1210by the gauge length 1225. The anvil 1215 can displace this portion suchthat the portion triggers a force measurable by the strain gauge 1220.The gauge length 1225 can be about 5 mm. The anvil 1215 can have awidth, for example, about 2 mm, resulting in a minimum gauge length ofabout 3 mm. The length can vary depending on the testing system.

The bending stiffness (Elastic modulus×area moment of inertia) can becalculated according to the equation EI=FL³/3δ, where F is deflectionforce, L is gauge length, and δ is deflection. For example, using a 3 mmgauge length (L=3 mm) and deflecting a tip of the catheter 2 mm (δ=2mm), 0.05-0.5 N of force can be generated. In some implementations, thedistal-most end of the distal luminal portion can range in bendingstiffness between 0.225-2.25 N-mm². As a comparison, the flexibility ofthe catheter advancement element 300 based on similar deflectionmeasurements and calculations can be as follows. Upon 2 mm deflectionand force gauge length of 3 mm, the distal tip of the catheteradvancement element 300 can range in bending force between 0.005-0.05 Nor can range in bending stiffness between 0.0225-0.225 N-mm². Otherprocedural catheters described herein can have a similar flexibilityranges providing a variable relative stiffness that transitions from theproximal end towards the distal end of the catheter as will be describedelsewhere herein.

FIGS. 13A-13B illustrate, in schematic, points along the catheter systemthat can be tested using the testing system shown in FIG. 12. The pointsmay vary depending on the overall size of the catheter system. Thevarious points of catheter system 150 can be tested when the cathetersystem 150 is placed in an advancement configuration. The catheter 200can have a lumen and a distal end having an opening from the lumen 223.The lumen can have an inner diameter at the distal end that is at leastabout 0.052″. The tubular portion 360 of the catheter advancementelement 300 can have an outer diameter having at least one snug point,where a difference between the inner diameter and the outer diameter atthe snug point can be no more than about 0.010″. The at least one snugpoint can be the point on the catheter advancement element 300 locatedjust proximal to the tapered distal tip 346. When the catheteradvancement element 300 is in the advancement configuration and ispositioned coaxially within the lumen of the distal luminal portion 222of the catheter 200, the at least one snug point of the tubular portion360 can substantially align with the distal end of the catheter 200.When in this configuration, the distal tip portion 346 of the catheteradvancement element 300 extends distal to the distal end of the catheter200. In some implementations, the difference at the snug point is normore than about 0.010″ or between about 0.006″ and 0.008″.

The tubular portion 360 of the catheter advancement element 300 can havea radiopaque marker band embedded within or positioned over a wall ofthe tubular portion 360 near the distal end region. A first radiopaquemarker band 344 a can be found at the distal end of the tapered tipportion 346 and a second radiopaque marker band 344 b can be found atthe proximal end of the tapered tip portion 346. The proximal radiopaquemarker band 344 b can have a proximal edge, a distal edge, and a widthbetween the proximal and distal edges. When in the advancementconfiguration, the proximal edge of the radiopaque marker band 344 b canalign substantially with the distal end of the distal, catheter portion222 such that the radiopaque marker band 344 b remains external to thelumen 223 of the distal, catheter portion 222. At least a portion of theradiopaque marker band 344 b can be positioned at the snug point, or thepoint of the catheter advancement element 300 where the outer diameteris no more than about 0.010″, preferably between about 0.006″ and 0.008″smaller than the inner diameter of the catheter 200 it is positionedwithin. The at least one snug point of the tubular portion 360 can belocated proximal to the tip portion 346 and can be where the taper ofthe tip portion 346 substantially ends. This allows for full extensionof the tapered tip portion 346 outside the distal end of the catheter200 and the snug point aligned substantially within the distal openingfrom the lumen 223 of the distal, catheter portion 222 therebyminimizing any distal-facing lip that might be created by the catheter200. The snug point can be located along at least a portion of a lengthof the outer diameter of the tubular portion 360 that has a length of atleast about 5 cm up to about 10 cm, the outer diameter beingsubstantially uniform or non-uniform.

The tip portion 346 can include at least three points (see, e.g., P1,P2, P3 of FIGS. 13A-13B) spaced along the length of the tip portion. Thedistal point P1 of the at least three points can be located a distanceproximal from the distal-most end of the catheter advancement element300. The distance can be a minimum distance needed to create a gaugelength for the testing system, for example at least about 3 mm to about5 mm. An intermediate point P2 of the at least three points can belocated a distance proximal to the distal point P1. A proximal point P3of the at least points can be located a distance proximal to theintermediate point P2. Additional points can be measured on the taperedtip portion 346 and that these are provided as illustrative.

FIG. 13A also illustrates points that can be tested on the system 150 asa whole. The coaxial catheter system 150 in the advancementconfiguration can include at least two system points along a length ofthe coaxial system 150. A first system point S1 of the at least twosystem points can be located proximal to the distal end of the catheter200. The first system point S1 generally takes into account the combinedbending force of the catheter 200 and the bending force of the catheteradvancement element 300 extending through the catheter 200 (see hashedline in FIG. 13B). The first system point S1 can be located proximal tothe distal end of the catheter 200 by a gauge length of about 5 mm. Asecond system point S2 of the at least two system points can be locateddistal to the first system point S1, for example, by a distance that isat least about 1 mm distal to the distal end of the catheter portion.The second system point S2 can take into account the bending force ofthe catheter advancement element 300 extending outside the catheter 200.The second system point S2 is illustrated in FIG. 13A as being adifferent point from P3, but the second system point S2 can be the sameas the proximal portion P3 or the same as another point such as P4. Thepoints are provided for illustrative purposes and are not intended to belimiting. Other points are considered herein.

FIG. 13B illustrates theoretical bending forces (N) of a catheter system150 at various points along a length of the system 150. The at leastthree points on the tip portion 346 include P1, P2, P3, and also P4spaced along the length of the tip portion 346 of the catheteradvancement element 300 (represented by a hash-dot-hash line). Each ofthese points can be located distal to the distal end of the catheter 200(solid line) when in the advancement configuration and, as such, takeinto account the bending force of only the catheter advancement element300. A fifth point P5 along the length of the catheter advancementelement 300 is also shown in FIG. 13B and can be at a locationpositioned inside the catheter 200 when the system 150 is in theadvancement configuration. P5, however, takes into account the bendingforce measurement of only the catheter advancement element 300.

The catheter 200 and catheter advancement element 300 can each have anyof a variety of material transitions from distal end towards theproximal end such that when the catheter advancement element 300 ispositioned coaxially within the catheter 200 in the advancementconfiguration, the flexibility of the system 150 transitions linearlyfrom the flexibility of the distal tip of the catheter advancementelement 300 towards more proximal regions of the system 150. In otherwords, the transition in flexibility from distal tip 346 of the catheteradvancement element 300 (positioned external to the distal end of thecatheter 200 when in the advancement configuration) to the flexibilityof the system 150 as a whole (i.e. catheter advancement element 300 plusthe catheter 200) can be defined by a slope that includes no significantstep increase and is substantially constant.

FIG. 13B illustrates this additive stiffness of the system 150 movingproximally along a length of the system 150. FIG. 13B shows the distalend of the catheter advancement element 300 at P1 has a bending forcethat is significantly lower than the bending force of the distal end ofthe catheter 200 through which it extends (e.g. greater than at leastabout 2×). In some implementations, the bending force of the distal endof the catheter advancement element 300 at P1 is no more than about 0.05N. The bending force of the catheter advancement element 300 canincrease over the length of the distal tip portion 346 to approach thehigher bending force of the distal end of the catheter 200. For example,the distal tip portion 346 can increase in stiffness over its length byat least 2× to approach the higher bending force of the distal end ofthe catheter 200. The bending force of the catheter system 150 over itslength can have a generally constant slope. This generally constantslope of increasing bending force for the distal tip portion of thecatheter advancement element 300 (shown as a hash-dot-hash line in FIG.13B) can transition to a generally constant slope of increasing bendingforce for the combined system 150 (shown as a hashed line in FIG. 13B)such that there is no significant step-up or change in slope between thetwo. The bending force of the distal tip portion 346 can have a constantslope up to where it transitions to the constant slope of the system 150as a whole (i.e. additive bending force between catheter 200 andcatheter advancement element 300 shown by hashed line). The bendingforce of the catheter advancement element 300 can continue to increasealong a length of the tip portion 346 (e.g. from P1 to P2 to P3 to P4)and then decrease again, for example, proximal to the at least one snugpoint (e.g. see P5 of FIG. 13B). The bending force of the catheteradvancement element 300 can decrease proximal to this snug point andremain significantly lower than the bending force of the catheter 200over a length. In some implementations, a proximal marker band 344 bidentifying the proximal end of the tapered distal tip 346 of thecatheter advancement element 300 can locally increase stiffness of thecatheter advancement element 300 at this point (e.g. near P3, P4, S2 ofFIG. 13B) thereby minimizing the step-up in stiffness from the distaltip portion 346 of the catheter advancement element 300 to the distalend of the catheter 200 of the assembled system 150. Tables 1, 3, 4, and5 of Example 1 in the Experimental section below describes the bendingforces of the various points along a length of different cathetersystems.

The bending forces along the length of the catheter system 150 can beused to calculate slopes of various segments of the system 150. Adifference between the bending force of P2 and the bending force of P1divided by the distance between P2 and P1 and/or a difference betweenthe bending force of P3 and the bending force of P2 divided by thedistance between P3 and P2 can provide a first flexibility slope. Adifference between the bending force of P3 and the bending force of P2divided by the distance between P3 and P2 can provide a secondflexibility slope. An average of the first flexibility slope and thesecond flexibility slope can define an average tip portion flexibilityslope. In some implementations, a fourth distal tip point can bemeasured such that the average tip portion flexibility slope can takeinto account this additional segment in calculating the average slope(e.g. segment between P3 and P4). A difference between the bending forceof S1 and the bending force of S2 (whether P3 or P4) divided by thedistance between S1 and S2 (whether P3 or P4) can provide a first systemflexibility slope.

In some implementations, the bending force of the distal end of thecatheter advancement element 300 can be no more than about 0.05 N. Theaverage tip portion flexibility slope can be at least about 0.005 N/mm.The system flexibility slope can be between about 0.01 N/mm to about0.03 N/mm. A ratio between the system flexibility slope to the averagetip portion flexibility slope can be less than about 25, less than about15, and preferably less than about 5, such as about 3 down to about 1.The slopes can be substantially constant or close to constant andsubstantially devoid of step-increases in bending force slope from onesegment to the next along the length of the catheter system 150. Inparticular, the catheter systems described herein avoid largestep-increases in slope from the flexibility of the portion extendingdistal to the distal end of the catheter and the flexibility of thesystem as a whole (see also FIGS. 14A-14D described below in Example 1).

The bending force of the distal tip of the catheter advancement element300 at P1 can be a fraction of the bending forces of the distal end ofthe catheter 200, such as between about 5%-15%. In contrast, the bendingforce of the snug point on the catheter advancement element 300 near theproximal end of the distal tip 346 (e.g., P3 or P4 or S2) can be about50%-90% the bending force (or flexibility) of the distal end of thecatheter 200. Thus, the bending force at the snug point of the catheteradvancement element 300 can be closer to the bending force of the distalend of the catheter 200. In some implementations, a portion of thecatheter advancement element 300 that is proximal to the tapered distaltip 346 can have a length of about 5 cm to about 10 cm and this portioncan have a bending force (or flexibility) that can be about 40%-90% thebending force of the distal end of the catheter 200.

The smooth transition in flexibility over the length of the cathetersystems described herein provide optimum navigability without risk ofkinking. The catheter systems described herein can have a distal endthat is exceptionally flexible and transition towards a proximal endthat is exceptionally stiff for optimum torqueing and manipulation.Thus, the bending force of P1 of the catheter advancement element 300can be a fraction of a bending force of a portion of the proximalportion 366 of the catheter advancement element 300. The proximalportion 366 can include at least one stiffness point that is withinabout 20 cm proximal to the tubular portion 360. The stiffness point canhave a bending force that is relatively high, for example, between about5 N up to about 15 N. A ratio of the bending force of the at least onestiffness point to the first bending force of P1 can be at least about100, at least about 200, or at least about 300. The proximal portion 366of the catheter advancement element 300 can be more than 300 timesstiffer than the distal tip P1 of the catheter advancement element atP1. The bending force of the catheter advancement element 300 at thedistal tip P1 can be no more than about 0.30% of the bending force ofthe proximal portion 366, for example between 0.10% to about 0.50%.

Methods of Use

In an implementation shown in FIG. 15, a guide sheath 400 can bedeployed such that the distal end of the sheath 400 is advanced to alocation in, for example, the internal carotid artery (ICA). The sheath400 can be advanced to the carotid artery over a guidewire and using anadvancement tool. The guidewire and advancement tool, if used, can beremoved or exchanged for a smaller guidewire that can be advancedfurther distal into the cerebral vessels or no guidewire at all asdescribed in more detail below. A first catheter 200 a can be advancedthrough the working lumen of the guide sheath 400 and out the distalend. The first catheter 200 a can have a distal luminal portion 222 acoupled to a proximal control element 230 a. The proximal controlelement 230 a can have a smaller outer diameter compared to the outerdiameter of the distal luminal portion 222 a and can be coupled near aproximal opening from the lumen of the distal luminal portion 222 a. Thefirst catheter 200 a can be advanced using a catheter advancementelement and without the help of a guidewire. The catheter advancementelement can aid the advancement of the first catheter 200 a through thevessel without hanging up on a severe angulation and/or a branchingvessel. The first catheter 200 a can be advanced through the workinglumen of the guide sheath 400 and then through the vessel to a firsttarget location. The catheter advancement element 300 can be removedfrom the lumen of the first catheter 200 a. A second catheter 200 bhaving a second catheter advancement element 300 can be advanced throughthe lumen of the first catheter 200 a. The second catheter 200 b canalso include a distal luminal portion 222 b coupled to a proximalcontrol element 230 b near a proximal opening from the lumen of thedistal luminal portion 222 b. Similar to the first catheter 200 a, theproximal control element 230 b of the second catheter 200 b can have asmaller outer diameter compared to the outer diameter of the distalluminal portion 222 b. The distal end of the second catheter 200 b canbe extended using its proximal control element 230 b to extend past thedistal end of the first catheter 200 a such that the smaller diametersecond catheter 200 b can reach a target site located to a distal vesselhaving a narrower dimension than the location of the first catheter 200a. In this implementation, the first spined catheter 200 a can act as asupport catheter for the second spined catheter 200 b. The secondcatheter 200 b can be advanced with or without a guidewire in place.Upon removal of the second catheter advancement element 300, the innerlumen of the second spined catheter 200 b can fluidly communicate withthe inner lumen of the first spined catheter 200 a that fluidlycommunicates with the working lumen of the guide sheath 400 forming acontiguous lumen formed of three sections of increasingly largerdimensions towards the proximal end of the catheter system. For example,the first catheter 200 a can have a distal luminal portion 222 a havingan inner diameter of about 0.088″ and the second catheter 200 b can havea distal luminal portion 222 b having an inner diameter of about 0.070″.More than two nested spined catheters is considered and that theirrespective inner and outer diameters are sized to receive one anotherfor use together. The corresponding ID and OD of the catheters can besized such that they slide relative to one another, but still providesufficient sealing. For example, the contiguous lumens created by thenested arrangement can seal against one another such that aspiration canbe drawn through them and an appropriate pressure can be applied throughthe nested catheters to accomplish, for example, aspiration forcesufficient for aspiration embolectomy of distant clots.

The proximal end of the nested catheter system can incorporate variousgripping, organizing, and attachment features. For example, the guidesheath 400 can include a proximal end coupled to a rotating hemostaticvalve 434 that provides access to the working lumen through which thecatheters can be inserted. Each of the components of the catheter systemcan extend proximally out from the valve 434. For example, the proximalcontrol elements 230 a, 230 b of the catheters 200 a, 200 b can extendthrough the valve 434. Proximal extensions of their respective catheteradvancement elements (not shown in FIG. 15) can also extend proximallythrough the valve 434. Each of these components in the nesting ortelescoping catheter set can incorporate identifying features at theirproximal end regions that distinguish them from one another. Forexample, each proximal control element 230 a, 230 b can include a tab234 a, 234 b having a distinguishing shape, color, or other visualcharacteristic that is unique to that particular catheter. Each proximalcontrol element 230 a, 230 b can include a coupling feature, such as aclip or other connector, that organizes the various control elements andprevents entanglement. Nesting catheters and their respective catheteradvancement elements can be incorporated within a kit.

The systems described herein contemplate using a base sheath and acatheter that can pass through the sheath and having sufficient lengthto reach the intracerebral target, such as the M1 segment of the middlecerebral artery. The use of a delivery catheter or catheter advancementelement with a tapered tip allow for large bore catheter delivery offull-length “over-the-wire” catheters or catheters such as thosedescribed herein having a proximal extension. The catheter advancementelement can include a pair of radiopaque markers configured to aid theoperator in delivery of the system. The distal marker near thedistal-most end of the catheter advancement element can bedifferentiated from the distal marker on the catheter by itscharacteristic appearance under fluoroscopy as well as by simply joggingback and forth the atraumatic catheter advancement element to understandthe relationship and positioning of the catheter advancement elementrelative to the catheter. The second marker on the catheter advancementelement that is proximal to the distal-most tip marker can delineate thetaper of the distal tip, i.e. where the outer diameter of the catheteradvancement element has a sufficient size to reduce the “lip” of thetransition between the catheter advancement element and the catheterthrough which it is inserted and configured to deliver. The markers aidin positioning the catheter advancement element relative to the distalend of the large-bore catheter such that the tip of the catheter isaligned with the taper of the catheter advancement element and the bestalignment is facilitated.

The relationship between the distal tip marker of the large-borecatheter is at or ideally just proximal to the taper marker of thecatheter advancement element (i.e. the proximal marker identifying thestart of the taper) is identifiable with the tandem marker system. Thepaired elements are in a “tip-to-taper” position. The relative extensionbetween the catheter advancement element and the catheter can beadjusted at the insertion of the system into the RHV. However, therelative extension can become altered with advancement through thesheath or guide catheter. As the system exits the guide catheter, thelarge bore catheter and the catheter advancement element can be adjustedto that the tip-to-taper position is assumed as the system traverses theoften tortuous proximal vessel (e.g. the cervical internal carotidartery) towards more distal targets. The system of the large borecatheter and the catheter advancement element can be locked into theirrelative extension so that the juxtaposition of the catheter advancementelement and the large-bore catheter is maintained. As the large-borecatheter is visualized within the sheath distal end or even slightlybeyond the distal end of the sheath, the catheter advancement elementcan be adjusted to assume the proper position relative to the catheterbefore advancement resumes. The optimum relative extension between thedistal marker of the catheter to the taper marker on the catheteradvancement element can be maintained through as much of the anatomy aspossible to maximize the delivery capability of the catheter advancementelement to navigate both tortuosity and to avoid side branches such asthe ophthalmic artery. Once the target is reached, the catheteradvancement element is then held fixed and the large-bore catheter thenadvanced over the catheter advancement element towards the targetwithout crossing the target.

The catheter advancement element is designed specifically such that thecatheter can be delivered without a need for a guidewire. This abilityto deliver without crossing the embolus and without a guidewire is basedupon the smooth transitions between the outer diameter of the catheteradvancement element and the large-bore catheter as well as the smoothtransition in flexibility between the two. When the catheter advancementelement is bent into an arc of greater than 180 degrees, the softnessand flexibility creates a smooth arc without severe bends or kinks inthe geometry of the catheter. Thus, the catheter advancement elementseeks the larger lumens and goes where the majority of blood flow goesas opposed to into the smaller branch arteries. The distal tip of thecatheter advancement element can facilitates a strong preference to seekout the larger vessels during advancement into the distal vessels. Thispropensity to stay within the main channel allows for the advancement oflarge bore catheters without the aid of a guidewire. The propensity tofollow the main channels of blood flow aligns with acute ischemic strokepathophysiology where major emboli tend to follow these same routes to apoint where the embolus lodges and interrupts antegrade blood flow. Aswell, these major channels are often ideal for placement of accesscatheters as these conduit arteries allow for smaller catheters to passinto specific target arteries for therapeutic intervention.

Standard neurovascular intervention, and nearly all endovascularintervention, is predicated on the concept that a guidewire leads acatheter to a target location. The guidewires are typically pre-shapedand often find side-branches of off-target locations where the guidewirewill bunch or prolapse causing time-consuming nuisances duringinterventions that often require repeated redirection of the guidewireby the operator to overcome. In addition, this propensity of a guidewireto enter side-branches can be dangerous. Guidewires are typically 0.014″to 0.018″ in the neuroanatomy and will find and often traumatize smallbranches that accommodate this size, which can lead to small bleeds ordissections and occlusion. In a sensitive area like the brain theseevents can be catastrophic. The tendency of a guidewire to bunch andprolapse can also cause a leading edge to the guidewire that can beadvanced on its own or as part of a triaxial system to create dissectionplanes and traumatize small vessels.

In contrast, the catheter advancement element described hereinpreferentially stays in the larger lumen of a conduit vessel. In thesetting of stroke treatment an embolus is driven to certain anatomiesbecause of the blood flow that the arterial system draws in the cerebralanatomy. The catheter advancement element tends to traverse a pathidentical to the path an embolus will take, particularly an embolusdriven from a location such as cardiac or carotid etiology. The catheteradvancement element delivers to the largest lumen within the anatomyeven in light of the highly tortuous anatomy and curves being navigated.The catheter advancement element can preferentially take the largerlumen at a bifurcation while also following the current of the greatestblood flow thereby maintaining the general direction and angulations ofthe parent vessel.

In viewing the standard anatomy found in the cerebral vasculature, theCircle of Willis is fed by two vertebral and two carotid conduitarteries. As these four arteries are the access points to the cerebralanatomy—the course of the catheter advancement element can be identifiedand has been validated in standard cerebral anatomy models. In theanterior circulation where the conduit artery point of entry forcerebral endovascular procedures is the internal carotid artery (ICA),the catheter advancement element can guide the large-bore catheter tothe M1 segment of the middle cerebral artery (MCA). The very flexiblenature of the catheter advancement element combined with the distalflexible nature of most cerebral catheters combine to allow deliverythrough severe tortuosity. Independent of the tortuous nature of thecourse of the arteries, the catheter advancement element tends tonavigate the turns and deliver to the largest offspring from a parentartery, for example, ICA to M1 segment of the MCA. The M2 levelbranching of the M1 can be variable, but is often seen to have two majorM2 branches (superior and inferior) and, depending on the anatomy, whichcan vary significantly between patients, may be seen to bifurcate“equally” or “unequally.” If the caliber of the M2 branching is ofsimilar size and angulation, the catheter advancement element may takeone of the two branches. If the target for catheter placement is not ina favorable angulation or size of artery, the catheter advancementelement may need to be curved (e.g. via shaping of a malleable distaltip) and directed or a guidewire may be used.

In some anatomies where the M2 bifurcation is “even” in size, aback-and-forth motion may aid in selecting one branch then the otherwhile still avoid the need or use of a guidewire or a curved distal tipof the catheter advancement element. The back-and-forth motion can allowfor the catheter advancement element to be directed into either branchof the M2. The catheter advancement element, even when initiallystraight, achieves some curvature that aids in directing it into abranch vessel. Thus, when an operator encounters an M2 bifurcation andthere is a desire to cannulate either branch of an evenly dividedbifurcation, selection of either branch is possible using the catheteradvancement element without a guidewire.

Thus, main channels such as the ICA, the middle cerebral artery and itstributaries in the anterior circulation will naturally be the pathway ofpreference for the described catheter advancement element andsubsequence large-bore catheter delivery (via access from the ICA). Asimilar phenomenon can occur in the posterior circulation, which isaccessed via the vertebral arteries arising from the subclavian arterieson the right and the left. The catheter advancement element will takethe main channels in this circulation as well by traversing thevertebral arteries to the basilar artery and to the major tributaries ofthe basilar: the posterior cerebral artery and superior cerebellararteries in the posterior circulation.

Navigation using the catheter advancement element can provide maximaldeliverability with minimal vascular trauma. Catheters can cause“razoring” effects in a curved vessel because the blunt end of a largebore catheter can tend to take the greater curve in rounding a vesselwhen pushed by the operator. This blunt end can gouge or “razor” thegreater curve with its sharp edge increasing the risk for dissectionalong an anatomic plane within the multilayered mid- or large-sizedartery or vein (see, e.g. Catheter Cardiovasc. Interv. 2014 February;83(2):211-20). Placement of a partially-inflated balloon and guidewirethrough the catheter in this setting can mitigate this “razor” effect bytaking the edge off the large-bore catheter. Similarly, the catheteradvancement element can serve to minimize the edge of these catheters.Positioning the catheter advancement element within the lumen of thelarge-bore catheter such that the taper marker of the catheteradvancement element is aligned optimally with the distal tip marker ofthe catheter minimizes the edge and thereby eliminates “razoring” as thelarge-bore catheter is advanced through turns of the vessel. This isparticularly useful for the cerebral anatomy. Stroke treatments aretypically needed in regions distal to the carotid siphon, particularlydistal to the ophthalmic artery takeoff from the greater curve of thesevere tortuosity of the final turn of the carotid siphon “S-turn”, the“anterior genu” of the carotid siphon typically seen as part of theterminal internal carotid artery (ICA). The specifics of the catheteradvancement element in proper alignment within the large bore catheter(the “tip-to-taper” position noted by the distal tip marker) relative tothe taper marker of the catheter advancement element maximize thelikelihood that razoring and hang-up on the ophthalmic artery areavoided. The taper marker of the catheter advancement element can bepositioned at or past the take-off of the ophthalmic artery to minimizethese deleterious effects and allows the large-bore catheter to pass theophthalmic artery without incident. In a relatively straight segment,which is common after passing the siphon, the large-bore catheter can beadvanced over the catheter advancement element, which serves still as aguiding element to the target. The transition between the catheteradvancement element and the distal edge of the large-bore catheter isinsignificant, especially compared to the step changes present with atypical microcatheter or guidewire, which do not prevent hand-ups onbranches such as the ophthalmic artery. The catheter advancement elementallows for maneuvering of the large-bore catheter clear to the face ofthe embolus without use of a microcatheter or guidewire and withoutcrossing and/or fragmenting the embolus in any way.

Conventional techniques to treat AIS whether with a stent retriever,aspiration techniques, or a combination of the two, require crossing thetarget occlusion with a guidewire and a microcatheter. Crossing of theembolus with a guidewire and then microcatheter can create fragmentationof the occlusion, which can be friable and thrombotic in nature. Thus,an aspiration technique where the embolus is removed en toto without anycrossing of the occlusion with any device is advantageous.

A stent retriever cannot cross or engage the target occlusion withoutthe “unsleeving” of the stent retriever across the embolus. ADAPT is afrontline aspiration-only technique that avoids crossing the targetocclusion with a stent retriever thereby lessening the risk offragmentation. However, the ADAPT approach still requires crossing thetarget occlusion with both a guidewire and microcatheter (see Turk etal. J. Neurointerv. Surg. 2014 Apr. 1; 6(3):231-7). A guide cathetersuch as Neuron Max (Penumbra) is positioned as distally as possible. Amicrocatheter and a micro guidewire are advanced through the guidecatheter and distal to the occlusion. Using the microcatheter and microguidewire as support, a reperfusion catheter such as Penumbra 5 Max isadvanced to the occlusion. Aspiration is applied until the occlusioncorks or wedges within the tip of the reperfusion catheter. Thereperfusion catheter is withdrawn and removed while maintainingaspiration and the occlusion within the catheter tip.

The systems described herein need not incorporate a guidewire ormicrocatheter. And, if a guidewire and microcatheter are used, they neednot be advanced to cross the target occlusion. Thus, the systemsdescribed herein can incorporate relatively large bore catheters thatare delivered without disturbing the target occlusion, reducing the riskfor stroke and downstream effects from fragmentation of the occlusion,and having improved efficiency. Additionally, the systems describedherein are single-operator systems allowing the operator to work at asingle RHV and, in the case of spined components, can manipulate all theelements being used to navigate the anatomy with single-handed“pinches.” This is sometimes referred to as “monopoint.”

As described above, the catheter advancement element can be arrangedcoaxially within the single lumen of the distal catheter portion forminga coaxial catheter system. The catheter can have a distal, catheterportion and a proximal extension. The distal, catheter portion can havean inner diameter defining the single lumen and a distal end defining adistal opening from the lumen. The proximal extension can be coupled toand extend proximally from the distal, catheter portion. The catheteradvancement element can have a tubular, polymeric portion having aninner diameter defining a lumen, a first outer diameter that issubstantially uniform along a length, and a radiopaque marker bandembedded within or positioned over a wall of the tubular, polymericportion. The radiopaque marker band can create a second outer diameterthat is located distal to and that is larger than the first outerdiameter. A tapered, polymeric tip can be located distal to the secondouter diameter that terminate at a distal opening from the lumen of thetubular portion. The tapered, polymeric tip can have a length that isbetween about 0.5 cm up to about 4 cm, for example, between about 1 cmand about 3 cm, or about 2.5 cm. The catheter advancement element canalso include a proximal extension coupled to and extending proximallyfrom the tubular, polymeric portion.

The coaxial catheter system can have an advancement configuration wherethe tapered, polymeric tip of the catheter advancement element extendsdistal to the distal end of the distal, catheter portion and theradiopaque marker band is substantially aligned with the distal end ofthe distal, catheter portion, and the first outer diameter is positionedwithin the lumen of the distal, catheter portion.

The operator can work from a single RHV of the guide sheath tomanipulate both the catheter and the catheter advancement element. Thecoaxial catheter system can be advanced together, maintaining theadvancement configuration. The relative relationship between theradiopaque marker band on the catheter advancement element and a secondmarker band near the distal end of the catheter can aid in maintainingthe advancement configuration during delivery. The operator can hold thetwo in relative position to one another using a single pinch and advancethis coaxial catheter system.

The coaxial catheter system can be advanced as far distal as possibleuntil the catheter advancement element is positioned at the face of theembolus. The proximal extension of the catheter advancement element canbe held “fixed” at the RHV and the catheter advanced over the catheteradvancement element so that the distal end of the distal, catheterportion is advanced over the catheter advancement element to the face ofthe embolus. No guidewire or microcatheter is needed to advance thecoaxial catheter system to the face of the embolus. Importantly, nodevices need cross the embolus.

The catheter advancement element can then be withdrawn from the coaxialcatheter system and removed from the single RHV while the catheter isheld in position at the face of the embolus. The system is ready forinitiation of aspiration as will be described in more detail below.

In some implementations, the first coaxial catheter system may not beable to reach the face of the embolus. Thus, the catheter advancementelement of the coaxial catheter system can be removed leaving the lumenof the distal, catheter portion open for advancing a second coaxialcatheter system through the first catheter. The second coaxial cathetersystem can include a second catheter and a second catheter advancementelement and be advanced similarly as the first coaxial catheter system(i.e. via monopoint manipulations), but through the first catheteracting as a support catheter.

Once the catheter is in position at the face of the embolus, the RHV canbe sealed and aspiration initiated through the same RHV such as via aside-arm. The embolus can be aspirated from the body through thecatheter via the aspiration pressure alone. Alternatively, the catheterhaving the embolus corked at the distal opening of the catheter can beslowly withdrawn, for example towards a lumen of a larger bore catheter,as aspiration is applied to effect embolus removal.

Withdrawing an embolus corked at the distal opening of the catheter backto the distal opening of the guide sheath can increase the risk offragmentation and embolization depending on the distance it must bewithdrawn before being fully encapsulated within a lumen. Thus, it isdesirable to use a nested system of successively larger catheter sizesto create a family of aspiration catheters all working from a singlepoint of operation via the single RHV. This allows for the smallest borecatheter advanced most distal to withdraw only a short distance into alarger bore catheter, which in turn can suction the embolus en toto, or,if needed, be withdrawn another short distance into a larger borecatheter that can suction the embolus from the body. The likelihood ofthe captured clot from fragmenting is thereby reduced and the likelihoodof the clot being aspirated en toto is increased.

The guide sheath can be a large 7F sheath configured to receive a largerbore catheter having an inner diameter of approximately 0.088″, which inturn can receive an intermediate bore catheter having an inner diameterof approximately 0.070″, which in turn can receive a smaller borecatheter having an inner diameter of approximately 0.054″. Any of avariety of sizes is considered herein and that these examples are notintended to be limiting.

Although the larger bore catheter can more efficiently capture theembolus by aspiration, there is a possibility that the substantiallylarger dimension of the larger bore catheter can prevent it beingadvanced to reach the embolus without additional manipulations. In someimplementations, a smaller bore catheter extending through the lumen ofthe larger bore catheter can be advanced to the face of the embolus. Thesmaller bore catheter (and its catheter advancement element) can be heldfixed such that the larger bore catheter is advanced over the smallerbore catheter as distal as possible. If the larger bore cathetercrawling over the smaller bore catheter is able to reach the embolus inthis way, the catheter advancement element can be removed from thesmaller bore catheter, the RHV closed to a seal, and aspirationinitiated. Both the distal end of the smaller bore catheter and thedistal end of the larger bore catheter are positioned at the face of theembolus. The smaller bore catheter can be removed from the system undercontinuous aspiration. If free flow is established with aspiration (e.g.as seen by the flow into the aspiration source), the operator can leavethe larger bore catheter in place and consider whether to performangiography to confirm establishment reconstitution of antegrade flowand resolution of the obstruction after insuring that the large-borecatheter is completely free of debris with aggressive aspiration andflushing. If free flow is not established, the aspiration can becontinued and removal of the smaller bore catheter can be followed byremoval of the larger bore catheter thereby removing the embolus fromthe body using the higher flow and forces generated by the larger borecatheter under full aspiration without the smaller bore catheterpositioned within its lumen obstructing flow. A single, sharedaspiration source may be used during removal of both the smaller boreand the larger bore catheters.

If the larger bore catheter is not able to reach the target embolus bycrawling over the smaller bore catheter, the larger bore catheter andthe catheter advancement element for the smaller bore catheter can beheld fixed at the RHV such that the smaller bore catheter can beadvanced between them to the face of the embolus. The smaller borecatheter can then provide a rail for another attempt at advancing thelarger bore catheter towards the face of the embolus. These steps can berepeated in sequence to “inch” the larger bore catheter toward theembolus until both the distal end of the smaller bore catheter and thedistal end of the larger bore catheter are positioned near the face ofthe embolus such that aspiration embolectomy can be performed throughthem.

The smaller bore catheter can be attached to the embolus and withdrawthe embolus towards the larger bore catheter. Thus, where the embolusmay be too large to fully enter the lumen of the smaller bore catheterit may be engulfed or retrieved by the lumen of the larger borecatheter. The smaller bore catheter having embolus attached to thedistal end by aspiration can be withdrawn followed immediately bycapture and withdrawal of the embolus via the larger bore catheter underaspiration.

Tension can get stored in a catheter system advanced through tortuouscerebral anatomy. Downward and lateral forces may be created on thesupporting catheter system as the distal tip of the catheter meetsresistance. The entire system can propel forward as the distal tip ofthe catheter is released past these points of resistance. The resistancecan occur at the tortuosity in the vessel or at obstructions orbifurcations or due to preexisting implants or other causes. Typically,the tension is stored without loss of position. The resultant effect isa back-and-forth type movement of the system to reach the target and thesteady storage of tension in the guide sheath as it is relentlesslypushed downward (i.e. proximally back against the direction ofinsertion).

In the case of aspiration systems for stroke, the same stored tensioncan occur with advancement of a larger bore catheter (e.g. an 0.088″ IDcatheter). As the larger bore catheter develops stored tension and theoperator tries to advance it to the target embolus (e.g. in the M1branch of the MCA), the larger bore catheter traverses the anatomy in a“greater curve to greater curve” manner introducing an amount of slackin the system. The stored tension creates the resistance that causes acatheter to jam at a point and not reach a target. Should the largerbore catheter not reach the target, a smaller bore catheter can beadvanced to reach the embolus due to smaller diameter and betterdeliverability. The smaller bore catheter can navigate the storedtension and also navigate the anatomy in a “greater curve to greatercurve” manner as the larger bore catheter did. The smaller bore cathetercan anchor onto the embolus via the aspiration pressure applied throughthe system. The smaller bore catheter can be fixed at the point ofocclusion and aspiration turned on to maximum (e.g. via a pump). Thisaffixes or anchors the smaller bore catheter to the embolus such thatthe operator can “straighten” the entire system and thereby apply aproximally-directed force on the smaller bore catheter to remove slackrelative to the surrounding anatomy while the distal end of the smallerbore catheter remains anchored onto the occlusion. The catheters oncethe slack is reduced now traverse the anatomy in a “lesser curve tolesser curve” manner rather than a “greater curve to greater curve”manner thereby straightening their course relative to the surroundinganatomy. A straightened course allows the larger bore catheter to beadvanced over the anchored smaller bore catheter such that its distalend can also reach the embolus target. Aspiration and anchoring throughthe smaller bore catheter is maintained and the operator creates astraighter, tension-free course to “rail” the larger bore catheterthrough it over the smaller bore catheter. Once the larger bore catheteris in place—even if the larger catheter does not reach theembolus—substantial embolic protection is afforded andoff-target-embolization avoided, particularly if the larger borecatheter is placed distal to the nearest bifurcation proximal to theembolus site.

Once the larger bore catheter is in position, the smaller bore catheterextending through it can be withdrawn. Aspiration may still be appliedby the single aspiration source and the seal between the corked embolusmaintained as the smaller bore catheter is withdrawn towards the distalend of the larger bore catheter. Once the smaller bore catheter ispulled into the distal end of the larger bore catheter, the aspirationpressure may be automatically turned on within the larger bore cathetersuch that the embolus is captured within the lumen of the larger borecatheter. Due to the larger inner diameter, the embolus under continuousaspiration pressure via the single, shared aspiration source will likelyevacuate the embolus. The smaller bore catheter and the larger borecatheter can both be withdrawn from the system.

Materials

One or more components of the catheters described herein may include orbe made from a variety of materials including one or more of a metal,metal alloy, polymer, a metal-polymer composite, ceramics, hydrophilicpolymers, polyacrylamide, polyethers, polyamides, polyethylenes,polyurethanes, copolymers thereof, polyvinyl chloride (PVC), PEO,PEO-impregnated polyurethanes such as Hydrothane, Tecophilicpolyurethane, Tecothane, PEO soft segmented polyurethane blended withTecoflex, thermoplastic starch, PVP, and combinations thereof, and thelike, or other suitable materials.

Some examples of suitable metals and metal alloys include stainlesssteel, such as 304V, 304L, and 316LV stainless steel; mild steel;nickel-titanium alloy such as linear-elastic and/or super-elasticnitinol; other nickel alloys such as nickel-chromium-molybdenum alloys(e.g., UNS: N06625 such as INCONEL® 625, UNS: N06022 such as HASTELLOY®C-22®, UNS: N10276 such as HASTELLOY® C276®, other HASTELLOY® alloys,and the like), nickel-copper alloys (e.g., UNS: N04400 such as MONEL®400, NICKELVAC® 400, NICORROS® 400, and the like),nickel-cobalt-chromium-molybdenum alloys (e.g., UNS: R30035 such asMP35-N® and the like), nickel-molybdenum alloys (e.g., UNS: N10665 suchas HASTELLOY® ALLOY B2®), other nickel-chromium alloys, othernickel-molybdenum alloys, other nickel-cobalt alloys, other nickel-ironalloys, other nickel-copper alloys, other nickel-tungsten or tungstenalloys, and the like; cobalt-chromium alloys; cobalt-chromium-molybdenumalloys (e.g., UNS: R30003 such as ELGILOY®, PHYNOX®, and the like);platinum enriched stainless steel; titanium; combinations thereof; andthe like; or any other suitable material and as described elsewhereherein.

Inner liner materials of the catheters described herein can include lowfriction polymers such as PTFE (polytetrafluoroethylene) or FEP(fluorinated ethylene propylene), PTFE with polyurethane layer(Tecoflex). Reinforcement layer materials of the catheters describedherein can be incorporated to provide mechanical integrity for applyingtorque and/or to prevent flattening or kinking such as metals includingstainless steel, Nitinol, Nitinol braid, helical ribbon, helical wire,cut stainless steel, or the like, or stiff polymers such as PEEK.Reinforcement fiber materials of the catheters described herein caninclude various high tenacity polymers like Kevlar, polyester,meta-para-aramide, PEEK, single fiber, multi-fiber bundles, high tensilestrength polymers, metals, or alloys, and the like. Outer jacketmaterials of the catheters described herein can provide mechanicalintegrity and can be contracted of a variety of materials such aspolyethylene, polyurethane, PEBAX, nylon, Tecothane, and the like. Othercoating materials of the catheters described herein include paralene,Teflon, silicone, polyimide-polytetrafluoroetheylene, and the like.

EXAMPLES

The catheter systems described herein were tested using a system such asthat shown in FIG. 12 for measuring bending forces and the data isprovided below. A first catheter system incorporated a catheteradvancement element having an outer diameter sized to extend through acatheter having an inner diameter of about 0.054″ (Version A). A secondcatheter system incorporated a catheter advancement element having anouter diameter sized to extend through a catheter having an innerdiameter of about 0.070″ (Versions B1 and B2). A third catheter systemincorporated a catheter advancement element having an outer diametersized to extend through a catheter having an inner diameter of about0.088″ (Version C).

At least three points along the tapered tip portion of the catheteradvancement elements were tested (see P1, P2, P3, P4 of FIGS. 13A-13B).The distal point P1 of the at least three points was located a distanceof about 5 mm proximal from the distal-most end of the catheteradvancement element. The second point P2 of the distal tip portion wasan intermediate point of the at least three points located a distanceproximal from the distal point P1. For Version A, the second point P2was about 12 mm proximal from the distal-most end of the catheteradvancement element. For Versions B1, B2, and C, the second point P2 wasabout 20 mm proximal from the distal-most end of the catheteradvancement element. A proximal point P3 of the at least points can belocated a distance proximal from the intermediate point P2 and was about13 mm proximal from the distal-most end of the catheter advancementelement for Version A and about 25 mm proximal for Versions B1, B2, andC. Some catheter system versions included a fourth point P4. P4 wasmeasured for both Versions B1, B2, and C at about 27 mm, 27 mm, and 28mm, respectively.

The catheter systems were placed in the advancement configuration andsoaked in a bath at 37° C. for a period of time prior to testing. Theadvancement configuration for the experiment is when the catheteradvancement element is positioned coaxially within the lumen of thedistal catheter portion of the catheter such that the at least one snugpoint of the tubular portion is substantially aligned with the distalend of the catheter and the distal tip portion of the catheteradvancement element extends distal to the distal end of the catheter.The region near P3 on the catheter advancement element formed a snugpoint with the catheter where the difference between the inner diameterand the outer diameter at the snug point was no more than about 0.010″.The difference was about 0.006″ for Version A and about 0.008″ forVersions B1 and C. Each of points P1, P2, P3, and P4 (where appropriate)were located on the tip portion of the catheter advancement element andextended distal to the distal end of the catheter.

A fifth point P5 was measured for all versions providing a bending forcefor the catheter advancement element only proximal to the snug point(see FIG. 13B). The fifth point P5 was at a location positioned insidethe catheter when the system is in the advancement configuration,however, P5 took into account the bending force measurement of only thecatheter advancement element. For Version A, this fifth point P5 wasmeasured about 16 mm proximal to the distal terminus of the catheteradvancement element. For Versions B1 and C, the fifth point P5 was about30 mm proximal to the distal terminus of the catheter advancementelement. When the components of the catheter system are in theadvancement configuration, this fifth point P5 on the catheteradvancement element can be located inside the catheter. Thus, P5 wasmeasured on the catheter advancement element without the catheter beingpresent.

At least two points along the catheter system were also tested tomeasure bending force of the system while in the advancementconfiguration (see S1 and S2 of FIGS. 13A-13B). The first system pointS1 took into account the combined bending force of the catheter and thebending force of the catheter advancement element extending through thecatheter and is represented by a hashed line in FIG. 13B. The firstsystem point S1 of the at least two system points was located proximalto the distal end of the catheter by a gauge length of about 5 mm orabout 19 mm from the distal-most terminus of the catheter system forVersion A and about 33 mm and 34 mm, respectively, from the distal-mostterminus of the catheter system for Versions B1/B2 and C.

A second system point S2 of the at least two system points was locateddistal to the first system point S1 by a distance. The second systempoint S2 took into account the bending force of the catheter advancementelement extending outside the catheter. In some tests, the second systempoint S2 was distal to the distal end of the catheter and was the sameas the proximal point P3 or the proximal point P4 (where available).

Table 1 below provides bending forces measured in Newtons (N) of thevarious points along the length of the catheter systems in theadvancement configuration. The points referred to in the table correlategenerally to the point shown in FIGS. 13A-13B, although are notrepresented to scale. The points are illustrative only and differentpoints can be measured.

TABLE 1 Catheter System Tested P1 P2 P3 P4 P5 S2 S1 Distal Tip Points(catheter advancement element only) System Points Version A 0.023N0.079N 0.087N n/a 0.061N 0.087N 0.208N 0.054” Distance along 5 mm 12 mm13 mm n/a 16 mm 13 mm 19 mm length of system from distal-most terminusVersion B1 0.025N 0.180N 0.211N 0.233N 0.155N 0.211N 0.442N 0.070”Distance along 5 mm 20 mm 25 mm 27 mm 30 mm 25 mm 33 mm length of systemfrom distal-most terminus Version B2 0.025N 0.180N 0.211N 0.233N 0.155N0.211N 0.345N 0.070” Distance along length of 5 mm 20 mm 25 mm 27 mm 30mm 25 mm 33 mm system from distal-most terminus Version C 0.088” 0.029N0.210N 0.245N 0.299N 0.219N 0.245N 0.415N Distance along length of 5 mm20 mm 25 mm 28 mm 30 mm 25 mm 34 mm system from distal-most terminus

Table 1 shows the bending force of the distal end of the catheteradvancement element at P1 was no more than about 0.05 N. A differencebetween the bending force of P2 and the bending force of P1 divided bythe distance between P2 and P1 and/or a difference between the bendingforce of P3 and the bending force of P2 divided by the distance betweenP3 and P2 provided a first flexibility slope. The first flexibilityslope was about 0.008 N/mm for Version A, 0.010 N/mm for Version B1, and0.012 N/mm for Version C. A difference between the bending force of P3and the bending force of P2 divided by the distance between P3 and P2provided a second flexibility slope. The second flexibility slope wasabout 0.008 N/mm for Version A, 0.006 N/mm for Version B1, and 0.007N/mm for Version C. An average of the first flexibility slope and thesecond flexibility slope defined an average tip portion flexibilityslope. In some tests, a fourth distal tip point was measured such thatthe average tip portion flexibility slope took into account thisadditional segment in calculating the average slope (e.g. segmentbetween P3 and P4). The average tip portion flexibility slope for eachversion of the catheter systems tested was at least 0.005 N/mm. Forexample, the average tip portion flexibility slope for Version A andVersion B1 was about 0.008 N/mm, and for Version C was about 0.010 N/mm.A difference between the bending force of S1 and the bending force of S2(whether P3 or P4) divided by the distance between S1 and S2 (whether P3or P4) provided a first system flexibility slope. The first systemflexibility slope using P3 as S2 was about 0.024 N/mm for Version A,0.013 N/mm for Version B1, and about 0.009 N/mm for Version C. In thiscalculation, a ratio between the first system flexibility slope to theaverage tip portion flexibility slope for Version A was about 3.0, theratio for Version B was about 1.6, and the ratio for Version C was about0.9. The first system flexibility slope using P4 as S2 was about 0.035N/mm for Version B1 and about 0.02 N/mm for Version C. In thiscalculation, a ratio between the first system flexibility slope to theaverage tip portion flexibility slope for Version B1 was about 4.4, andthe ratio for Version C was about 2.0. Regardless which point is usedfor S2 (whether P3 or P4), the ratio between the first systemflexibility slope to the average tip portion flexibility slope was lessthan about 5 for each version.

FIGS. 14A-14D illustrate the bending forces of the various pointsdescribed above versus distance in mm along a length of the system. FIG.14A illustrates data for Version A system incorporating a catheteradvancement element 300 having an outer diameter sized to extend througha catheter having an inner diameter of about 0.054″. FIG. 14Billustrates data for Version B1 system incorporating a catheteradvancement element 300 having an outer diameter sized to extend througha catheter having an inner diameter of about 0.070″. FIG. 14Cillustrates data for another version (Version B2) of a catheter systemincorporating a catheter advancement element 300 having an outerdiameter sized to extend through a catheter having an inner diameter ofabout 0.070″. FIG. 14D illustrates data for Version C systemincorporating a catheter advancement element 300 having an outerdiameter sized to extend through a catheter having an inner diameter ofabout 0.088″.

FIGS. 14A-14D illustrate how the slopes of the lines are substantiallyconstant or close to constant and substantially devoid of step-increasesin bending force slope from one segment to the next along the length ofthe catheter system. In particular, each of the versions tested had nostep-increases in bending force between the distal tip points (i.e. thepoints of the catheter advancement element extending distal to thedistal end of the catheter) and the system point (i.e. the combinationof the catheter and the catheter advancement element). As such, theoverall slope of the system when in the advancement configuration issubstantially constant over a length of the system, for example, alength being from a distal-most terminus (0 mm) to about 35 mm proximalto the distal-most terminus of the system.

In each version tested, the bending force of the distal end of thecatheter advancement element at P1 was significantly lower than thebending force of the distal end of the catheter through which it extends(e.g. greater than at least about 2×) (see also Table 4 below). Thebending force of the distal end of the catheter advancement element atP1 was no more than about 0.05 N. The bending force of the catheteradvancement element increased over the length of the distal tip portionto approach the higher bending force of the distal end of the catheter.For example, the distal tip portion increased in stiffness over itslength by at least 2× to approach the bending force of the distal end ofthe catheter. The bending force of the catheter system over its lengthhad a generally constant slope. This generally constant slope ofincreasing bending force for the distal tip portion of the catheteradvancement element (shown as a hash-dot-hash line in FIG. 13B)transitioned to a generally constant slope of increasing bending forcefor the combined system (shown as a hashed line in FIG. 13B) such thatthere is no significant step-increase in slope between the two. Thebending force of the distal tip portion had a slope that transitioned tothe slope of the system as a whole (i.e. additive bending force betweencatheter and catheter advancement element shown by hashed line) withouta significant step-increase in slope from one segment to the next.

Corresponding points on a different catheter system (GUIDELINERNavigational catheter system; Vascular Solutions, Minneapolis, Minn.)were tested as a comparison. The data is provided in Table 2 below andalso in FIG. 14E, which illustrates the bending force of the variouspoints versus distance in mm along a length of the GUIDELINER system.

TABLE 2 Catheter System P1 P2 P3 S2 S1 Distal Tip Points System(Navigational catheter only) Points 8F GUIDELINER 0.114N 0.137N 0.141N0.141N 0.636N Navigational catheter Distance along length 5 mm 10 mm 15mm 15 mm 20 mm of system from distal- most terminus

The first bending force of P1 was greater than 0.05 N, specificallyabout 0.114 N. Various calculations using the bending force data shownin Table 2 were performed. The first flexibility slope for theGUIDELINER system was about 0.005 N/mm. The second flexibility slope forthe GUIDELINER system was about 0.001 N/mm. The average tip portionflexibility slope for the GUIDELINER system was about 0.003 N/mm. Thefirst system flexibility slope for the GUIDELINER system was about 0.10N/mm. The ratio between the first system flexibility slope to theaverage tip portion flexibility slope for the GUIDELINER system wasgreater than 30. This ratio illustrates numerically what can be seengraphically in FIG. 14E. FIG. 14E shows the GUIDELINER catheter systemundergoes a large step-increase in slope from the flexibility of theportion of the navigation catheter extending distal to the distal end ofthe catheter through which it extends and the flexibility of the systemas a whole. These large step-increases in slope means that there aresharp transitions in stiffness along the length of the catheter systemthat prevent the GUIDELINER catheter system from being advanced aroundcurves of the tortuous vessels traversing the bony anatomy of the skull.The catheter tip is prevented from passing through such curves. Incontrast, the catheter systems described herein have smaller sloperatios, which illustrate they possess the smoothest possible transitionin stiffness from distal to proximal end and thus, are suitable fordelivery through tortuous anatomy.

Table 3 below shows slopes of the catheter systems described hereincompared to the slopes of the GUIDELINER Navigation Catheter system.“Average tip portion flexibility slope” was calculated. Morespecifically, the average tip portion flexibility slope is the averageof the slopes of segments P1 to P2, P2 to P3, and P3 to P4, whereavailable. Additional segments of the tip portion can be included.“Slope of segment S2-S1” is the slope of the segment between systempoints S2 and S1. The system point S2 can be the same point or adifferent point as one of the other points (e.g. P4 or P3). “Slope ofsegment P1-S1” is the slope of a line drawn from distal-most point P1directly to the system point S1.

TABLE 3 Average tip portion Slope of Slope of flexibility segmentsegment Catheter P1 P2 P3 P4 S2 S1 slope S2-S1 P1-S1 System (N) (N) (N)(N) (N) (N) (N/mm) (N/mm) (N/mm) Version A 0.023 0.079 0.087 n/a 0.0870.208 0.0080 0.0202 0.0132 0.054” Ratio to 1 2.52 1.65 average tipportion flexibility slope Version B1 0.025 0.180 0.211 0.233 0.233 0.4420.0093 0.0349 0.0149 0.070” Ratio to 1 3.76 1.61 average tip portionflexibility slope Version B2 0.025 0.180 0.211 0.233 0.233 0.345 0.00930.0187 0.0114 0.070” Ratio to 1 2.01 1.23 average tip portionflexibility slope Version C 0.029 0.210 0.245 0.299 0.299 0.415 0.01240.0193 0.0133 0.088” Ratio to 1 1.56 1.07 average tip portionflexibility slope GUIDELINER 0.114 0.137 0.141 n/a 0.141 0.636 0.00260.0990 0.0348 Navigation Catheter Ratio to 1 37.40 13.13 average tipportion flexibility slope

The tapered distal tip portion underwent a change in bending force overits length that was at least a 2-fold increase. The tapered distal tipportion of the catheter advancement element of Versions A, B1, B2, and Chad a minimum slope of at least 0.005 N/mm. In contrast, the GUIDELINERincrease in bending force over its length was only about 1.2 times.Further, the GUIDELINER had an average tip portion flexibility slopethat was less than about 0.003 N/mm. The slope of each of the cathetersystems (Versions A, B1, B2, and C) increased from distal point P1 tosystem point S1 no more than about 5 times whereas the GUIDELINERincreased by more than 30 times from 0.114.

Table 4 below shows the bending forces of the distal tip of the catheteradvancement element relative to the bending forces of the distal end ofthe catheter. The point measured and referred to in the table 4 below as“Catheter Point C1” was a point along a length of the catheter nearestthe distal end that is measurable using the systems described herein,for example, a gauge length of the catheter from the distal-most end ofthe catheter of at least about 5 mm. The bending force (or flexibility)of the distal tip at P1 was about 16% the bending force (or flexibility)of C1 for Version A, about 10% for Version B1 and about 8% for VersionC. Thus, the bending force at P1 was between about 5% and 15% thebending force at C1. The bending force (or flexibility) of the snugpoint near the proximal end of the distal tip (e.g., P3 or P4) was about59% for Version A, about 91% for Version B1, and about 82% for VersionC. Thus, the bending force at the snug point was between about 50% and90% the bending force (or flexibility) of C1. In contrast, the distaltip point P1 on the GUIDELINER was stiffer compared to the same point onversions A, B1, or C. The proximal point P3 on the GUIDELINER had agreater bending force compared to its distal tip point P1, but thisbending force was much lower compared to the bending force of thecatheter point C1 (i.e. only 23% the stiffness of the catheter pointC1). Thus, there was a larger difference between the bending force ofthe navigation catheter at P3 compared to the bending force of thecatheter at C1 compared to the versions of the catheter systemsdescribed herein. This difference contributes to the largerstep-increase in slopes of the GUIDELINER catheter system as bestvisualized in FIG. 14E,

TABLE 4 Distal Tip Proximal Point Catheter Point P1 P3/P4 C1 CatheterSystem (N) (N) (N) (Catheter Advancement Element only) Catheter onlyVersion A 0.023 0.087 0.147 0.054” 16% 59% 100% Version B1 0.025 0.2330.256 0.070” 10% 91% 100% Version C 0.088” 0.029 0.299 0.366  8% 82%100% 8F GUIDELINER 0.114 0.141 0.624 Navigational catheter 18% 23% 100%

Table 5 below shows the bending force of P1 of the catheter advancementelement relative to a bending force of a portion of the proximalextension of the catheter advancement element. Point E1 on the proximalextension that was selected for testing was within about 20 cm proximalto the tubular portion of the catheter advancement element. The point E1had a bending force that was about 9.21 N. The bending force of thecatheter advancement element at the distal tip P1 was no more than about0.30% of the bending force of the proximal extension at E1. The ratio ofthe bending force of point E1 to the first bending force at distal tippoint P1 was at least about 300. The proximal extension of the catheteradvancement element of Version C was about 318 times stiffer than thedistal tip of the catheter advancement element at P1, Version B1 wasabout 368 times stiffer, and Version A was about 400 times stiffer.

TABLE 5 Catheter P1 E1 % System (N) (N) stiffness Ratio Version A 0.0239.21 0.25% 400 0.054” Version B1 0.025 9.21 0.27% 368 0.070” Version C0.029 9.21 0.30% 318 0.088” GUIDELINER 0.114 17.52 0.65% 154 NavigationCatheter Orion-21 0.137 8.36 1.64% 61

Two other catheter systems were analyzed as a comparison. The bendingforce of the GUIDELINER navigation catheter at E1 was greater than anyof the versions tested at about 17.52N. The bending force of the distaltip at P1 was also higher compared to the catheter system versionsdescribed herein. The bending force of the navigation catheter at thedistal tip P1 was about 0.65% the bending force of the proximalextension at E1. Further, the bending force at point E1 of theGUIDELINER navigation catheter was only 154 times more than the distaltip P1. The ORION-21 catheter (Medtronic, Minneapolis, Minn.) had abending force at the distal tip P1 that was about 1.64% the bendingforce at E1. The bending force at point E1 of the ORION-21 was onlyabout 60 times stiffer than its distal tip at P1.

The data described herein provides a numerical picture of the smoothtransition in flexibility over the length of the various cathetersystems described herein that provides optimum navigability without riskof kinking. The catheter systems described herein have distal ends thatare exceptionally flexible that transition towards proximal ends thatare exceptionally stiff for optimum torqueing and manipulation. Thetransitions in flexibility along the length of the system are managedsuch that the two components work seamlessly together as if they were asingle component and without any large step-increases in stiffness fromone segment to another.

Implementations describe catheters and delivery systems and methods todeliver catheters to target anatomies. However, while someimplementations are described with specific regard to deliveringcatheters to a target vessel of a neurovascular anatomy such as acerebral vessel, the implementations are not so limited and certainimplementations may also be applicable to other uses. For example, thecatheters can be adapted for delivery to different neuroanatomies, suchas subclavian, vertebral, carotid vessels as well as to the coronaryanatomy or peripheral vascular anatomy, to name only a few possibleapplications. Although the systems described herein are described asbeing useful for treating a particular condition or pathology, that thecondition or pathology being treated may vary and are not intended to belimiting. Use of the terms “embolus,” “embolic,” “emboli,” “thrombus,”“occlusion,” “clot”, etc. that relate to a target for treatment usingthe devices described herein are not intended to be limiting. The termsmay be used interchangeably and can include, but are not limited to ablood clot, air bubble, small fatty deposit, or other object carriedwithin the bloodstream to a distant site or formed at a location in avessel. The terms may be used interchangeably herein to refer tosomething that can cause a partial or full occlusion of blood flowthrough or within the vessel.

In various implementations, description is made with reference to thefigures. However, certain implementations may be practiced without oneor more of these specific details, or in combination with other knownmethods and configurations. In the description, numerous specificdetails are set forth, such as specific configurations, dimensions, andprocesses, in order to provide a thorough understanding of theimplementations. In other instances, well-known processes andmanufacturing techniques have not been described in particular detail inorder to not unnecessarily obscure the description. Reference throughoutthis specification to “one embodiment,” “an embodiment,” “oneimplementation, “an implementation,” or the like, means that aparticular feature, structure, configuration, or characteristicdescribed is included in at least one embodiment or implementation.Thus, the appearance of the phrase “one embodiment,” “an embodiment,”“one implementation, “an implementation,” or the like, in various placesthroughout this specification are not necessarily referring to the sameembodiment or implementation. Furthermore, the particular features,structures, configurations, or characteristics may be combined in anysuitable manner in one or more implementations.

The use of relative terms throughout the description may denote arelative position or direction. For example, “distal” may indicate afirst direction away from a reference point. Similarly, “proximal” mayindicate a location in a second direction opposite to the firstdirection. The reference point used herein may be the operator such thatthe terms “proximal” and “distal” are in reference to an operator usingthe device. A region of the device that is closer to an operator may bedescribed herein as “proximal” and a region of the device that isfurther away from an operator may be described herein as “distal”.Similarly, the terms “proximal” and “distal” may also be used herein torefer to anatomical locations of a patient from the perspective of anoperator or from the perspective of an entry point or along a path ofinsertion from the entry point of the system. As such, a location thatis proximal may mean a location in the patient that is closer to anentry point of the device along a path of insertion towards a target anda location that is distal may mean a location in a patient that isfurther away from an entry point of the device along a path of insertiontowards the target location. However, such terms are provided toestablish relative frames of reference, and are not intended to limitthe use or orientation of the catheters and/or delivery systems to aspecific configuration described in the various implementations.

While this specification contains many specifics, these should not beconstrued as limitations on the scope of what is claimed or of what maybe claimed, but rather as descriptions of features specific toparticular embodiments. Certain features that are described in thisspecification in the context of separate embodiments can also beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment canalso be implemented in multiple embodiments separately or in anysuitable sub-combination. Moreover, although features may be describedabove as acting in certain combinations and even initially claimed assuch, one or more features from a claimed combination can in some casesbe excised from the combination, and the claimed combination may bedirected to a sub-combination or a variation of a sub-combination.Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults. Only a few examples and implementations are disclosed.Variations, modifications and enhancements to the described examples andimplementations and other implementations may be made based on what isdisclosed.

In the descriptions above and in the claims, phrases such as “at leastone of” or “one or more of” may occur followed by a conjunctive list ofelements or features. The term “and/or” may also occur in a list of twoor more elements or features. Unless otherwise implicitly or explicitlycontradicted by the context in which it is used, such a phrase isintended to mean any of the listed elements or features individually orany of the recited elements or features in combination with any of theother recited elements or features. For example, the phrases “at leastone of A and B;” “one or more of A and B;” and “A and/or B” are eachintended to mean “A alone, B alone, or A and B together.” A similarinterpretation is also intended for lists including three or more items.For example, the phrases “at least one of A, B, and C;” “one or more ofA, B, and C;” and “A, B, and/or C” are each intended to mean “A alone, Balone, C alone, A and B together, A and C together, B and C together, orA and B and C together.”

Use of the term “based on,” above and in the claims is intended to mean,“based at least in part on,” such that an unrecited feature or elementis also permissible.

What is claimed is:
 1. A coaxial catheter system, the system comprising:a catheter comprising: a distal, catheter portion having a lumen, and adistal end region, and a distal-most end having an opening from thelumen, the lumen having an inner diameter at the distal end region of atleast about 0.052″; and a proximal extension coupled to and extendingproximally from the distal, catheter portion, the proximal extensionbeing less flexible than the distal, catheter portion; and a catheteradvancement element comprising: a tubular portion having an innerdiameter that is at least about 0.014″ up to about 0.024″, an outerdiameter, wherein the outer diameter has at least one snug point,wherein a difference between the inner diameter of the distal, catheterportion and the outer diameter of the tubular portion at such snug pointis no more than about 0.010″; a proximal extension coupled to andextending proximally from the tubular portion, the proximal extensionbeing less flexible than the tubular portion; and a tubular, polymer tipportion located distal to the at least one snug point of the tubularportion, wherein the tip portion has a length and tapers along at leasta portion of the length of the tip portion, wherein the coaxial cathetersystem has an advancement configuration characterized by: a) thecatheter advancement element positioned coaxially within the lumen ofthe distal catheter portion, wherein the at least one snug point of thetubular portion is substantially aligned with the distal end region ofthe distal catheter portion, and b) wherein the tip portion in theadvancement configuration has at least three points spaced along thelength of the tip portion, the at least three points comprising: adistal point of the at least three points located a distance proximalfrom a distal-most end of the catheter advancement element, the distalpoint having a first bending force that is no greater than about 0.05Newtons; an intermediate point of the at least three points located adistance proximal from the distal point, the intermediate point having asecond bending force; and a proximal point of the at least three pointslocated a distance proximal from the intermediate point, the proximalpoint having a third bending force; and c) wherein the coaxial system inthe advancement configuration has at least two system points along alength of the coaxial system, the at least two system points comprising:a first system point of the at least two system points located proximalto the distal-most end of the catheter portion, the first system pointhaving a first system bending force; and a second system point of the atleast two system points located distal to the first system point by adistance that is at least about 1 mm distal to the distal-most end ofthe catheter portion, wherein the second system point can be the same ordifferent from the proximal point, the second system point having asecond system bending force, wherein a difference between the secondbending force and the first bending force divided by a distance betweenthe distal point and the intermediate point equals a first flexibilityslope; wherein a difference between the third bending force and thesecond bending force divided by a distance between the intermediatepoint and the proximal point equals a second flexibility slope; whereinan average of the first flexibility slope and the second flexibilityslope defines an average tip portion flexibility slope; wherein adifference between the first system bending force and the second systembending force divided by a distance between the first system point andthe second system point equals a third flexibility slope; and wherein aratio of the third flexibility slope to the average tip portionflexibility slope is less than about
 25. 2. The coaxial catheter systemof claim 1, wherein the proximal extension of the catheter advancementelement has at least one stiffness point located within about 125 cmfrom the distal-most end of the catheter advancement element, the atleast one stiffness point has a bending force, wherein a ratio of thebending force of the at least one stiffness point to the first bendingforce of the distal point is at least about
 100. 3. The coaxial cathetersystem of claim 1, wherein the proximal extension of the catheteradvancement element has at least one stiffness point located withinabout 125 cm from the distal-most end of the catheter advancementelement, the at least one stiffness point has a bending force, wherein aratio of the bending force of the at least one stiffness point to thefirst bending force of the distal point is at least about
 200. 4. Thecoaxial catheter system of claim 1, wherein the proximal extension ofthe catheter advancement element has at least one stiffness pointlocated within about 125 cm from the distal-most end of the catheteradvancement element, the at least one stiffness point has a bendingforce, wherein a ratio of the bending force of the at least onestiffness point to the first bending force of the distal point isgreater than at least about
 300. 5. The coaxial catheter system of claim1, wherein the length of the tip portion is at least about 1 cm up toabout 4 cm.
 6. The coaxial catheter system of claim 5, wherein a ratioof the third bending force of the proximal point to the first bendingforce of the distal point is at least
 2. 7. The coaxial catheter systemof claim 1, wherein a ratio of the first system bending force to thefirst bending force of the distal point is at least 2 and no more thanabout
 5. 8. The coaxial catheter system of claim 1, wherein the distal,catheter portion has a catheter point located a distance of at least 5mm proximal from the distal-most end, the catheter point having acatheter bending force.
 9. The coaxial catheter system of claim 8,wherein the first bending force of the distal point is about 5%-15% thecatheter bending force.
 10. The coaxial catheter system of claim 8,wherein the third bending force of the proximal point is about 50%-90%the catheter bending force.
 11. The coaxial catheter system of claim 1,wherein a difference between the first bending force at the distal pointto the third bending force at the proximal point is a function of wallthickness.
 12. The coaxial catheter system of claim 1, wherein the innerdiameter at the distal end region of the distal, catheter portion isabout 0.054″ and the difference at the snug point is about 0.006″ toabout 0.008″.
 13. The coaxial catheter system of claim 1, wherein theinner diameter at the distal end region of the distal, catheter portionis about 0.070″ up to about 0.088″ and the difference at the snug pointis no more than about 0.006″ to about 0.008″.
 14. The coaxial cathetersystem of claim 1, wherein the tubular portion of the catheteradvancement element has a radiopaque marker band embedded within orpositioned over a wall of the tubular portion, the radiopaque markerband positioned at the snug point.
 15. The coaxial catheter system ofclaim 14, wherein the radiopaque marker band has a proximal edge, adistal edge, and a width between the proximal edge and the distal edge,wherein, when in the advancement configuration, the proximal edge of theradiopaque marker band aligns substantially with the distal-most end ofthe distal, catheter portion such that the radiopaque marker bandremains external to the lumen of the distal, catheter portion.
 16. Thecoaxial catheter system of claim 1, wherein the outer diameter of thetubular portion has a length that is at least about 5 cm up to about 10cm, wherein the snug point is located along at least a portion of thelength.
 17. The coaxial catheter system of claim 16, wherein the outerdiameter is substantially uniform along the length.
 18. The coaxialcatheter system of claim 16, wherein the outer diameter is substantiallynon-uniform along the length.
 19. The coaxial catheter system of claim1, wherein the distal point is located a distance of at least 5 mmproximal from the distal-most end of the catheter advancement element.20. The coaxial catheter system of claim 1, wherein the first systempoint is located at least about 5 mm proximal to the distal-most end ofthe catheter portion.
 21. The coaxial catheter system of claim 1,wherein the coaxial catheter system when in the advancementconfiguration is configured to perform at least a 180 degree turnwithout kinking or ovalizing.
 22. The coaxial catheter system of claim21, wherein the at least a 180 degree turn of the coaxial cathetersystem maintains a folded width across 4.0 mm.
 23. The coaxial cathetersystem of claim 1, wherein the catheter advancement element comprises noseparate liner.
 24. The coaxial catheter system of claim 23, wherein atleast a distal portion of the tubular portion and the tubular, polymertip portion of the catheter advancement element comprise unreinforcedpolymer.
 25. The coaxial catheter system of claim 24, wherein theunreinforced polymer incorporates a lubricious additive.
 26. The coaxialcatheter system of claim 1, wherein the tubular portion and the tubular,polymer tip portion of the catheter advancement element have a length ofabout 10 cm to about 12.5 cm.
 27. The coaxial catheter system of claim1, wherein a ratio of the third bending force of the proximal point tothe first bending force of the distal point is at least 2, and wherein aratio of the first system bending force to the first bending force ofthe distal point is at least 2 and no more than about 5.